Thiazole ring- the antimicrobial, anti-inflammatory, and anticancer active scaffold

1 Introduction

Organic and medicinal chemistry are important majors in the field of synthesis and development of structures with biological activity (Sani and Zanda, 2022; Wentrup, 2022). In recent years, researchers focusing on structures that have scaffolds containing heterocycles atoms, and rings. There are a lot of molecules with five, six, and so on membered heterocycle rings containing hetero atoms (Kaur, 2018a,b; Kaur and Kishore, 2014); Kaur et al., 2021). Meanwhile, the thiazole ring is one of the types of heterocyclic rings with different biological properties (Ali and Sayed, 2021).Scheme 1.

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Scheme 1

The thiazole ring has the characteristic of resisting the inflammatory cells of various bacterial and fungal strains, as well as all types of cancer cells, and it can even be used to treat these pathogens in industrial drugs. Therefore, the thiazole ring is a suitable protective medicine for humans from these pathogenic agents.

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Research illustrates Thiazole rings have an excellent wide range of pharmaceutical applications such as antimalarial (Bueno et al., 2016), antifungal (Lino et al., 2018), anticancer (Jain et al., 2018), anti-inflammatory (Moldovan et al., 2011), antibacterial (Li et al., 2014), antioxidant (Grozav et al., 2017), and so on. According to the Njardarson group reports, five drugs with thiazole scaffold exist in the top two hundred brand name drugs by retail sales in 2015, namely: Viekira Pak, Sprycel, Augmentin, Kaletra, and Olysio/Sovriad. Five drugs exist in the top two hundred brand name drugs by retail sales in 2016, namely: Stribild, Sprycel, Genvoya, Myrbetriq, and Augmentin. In 2018, seven drugs exist in the top two hundred brand name drugs by retail sales, namely: Genvoya, Sprycel, Prezcobix, Myrbetriq, Tafinlar, Lixiana, and Augmentin. The number of drugs increased to eight in 2019, which are Genvoya, Sprycel, Prezista, Myrbetriq, Edoxaban, Tafinlar/Mekinist, Lixiana, and Augmentin. This trend decreased to 5 drugs in 2020, but again from 2021 this trend increased until it increased to 7 drugs in 2022. According to the information in the Fig. 1, it can be seen that after every decreasing trend, there is an increasing trend. Also, the highest number of drugs containing the thiazole ring was in 2019, and in 2015, 2016 and 2020, the number of drugs was fixed at 5 (Fig. 1) (J. Chem. Ed. 2010).

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Fig. 1

The number of drugs containing thiazole scaffold in between two hundred brand drugs by retail sales from 2015 to 2022.

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The purpose of the present review is to collect and analysis of important studies that investigate of antimicrobial, anti-inflammatory, and anticancer activity of structures that have thiazole scaffold from 2014 to 2022 and show their advance for more effectiveness.

2 Thiazole derivatives with antimicrobial activity

For a long time, we didn't have very many new drugs to treat bacteria. This led to a lack of drugs that work against bacteria that are resistant to drugs. So now we need to synthesize new drugs that work in different ways and that can treat both sensitive and resistant strains of bacteria (Holmes et al., 2016).

In 2014, Liaras and co-workers synthesized two thiazole-based aminopyrimidine derivatives and eight N-phenylpyrazoline derivatives (Fig. 2). Ten derivatives were tested against 9 g-positive and negative bacteria and 9 fungal strains. The evaluations showed all structures have antibacterial activities. In addition, two structures (1a and 1b) among all structures had excellent activity but had no good yield (15% − 27%) (Table 1 and Fig. 2). Streptomycin and ampicillin were used as reference drugs. Most of the derivatives showed comparable or better activities than the reference drugs. Among all derivatives, structure 1a had the best activity (Table 1 and Fig. 2). Structure 1b showed the best inhibitory effect against gram-positive bacteria (Table 1 and Fig. 2). The best antibacterial activity against gram-positive and negative bacteria showed by structure 1a (Table 1 and Fig. 2). In addition, structure 2d displayed The lowest antibacterial activity, and had no activity against En. cloacae. Also, all derivatives had potent activity against S. aureus and L. monocytogenes compared to streptomycin (except 2 g) (Table 1 and Fig. 2). In the case of 2a-h, structures 2e, 2f and 2 h just increased the activity in comparison structure 2a, while structures 2d and 2 g showed the opposite effect (Table 1 and Fig. 2) (Liaras et al., 2014)

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Fig. 2

Chemical structures 1a-b and 2a-h (Liaras et al., 2014)

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On the other hand, the antifungal activity of derivatives was tested in comparison to ketoconazole and bifonazole as reference drugs. Structure 1a had the best activity. In the case of A. Ochraceus structures 1b had the best activity (Table 1 and Fig. 2) (Liaras et al., 2014)

A series of structures containing thiazole scaffold was reported by Rostom and co-workers and evaluated their in vitro antibacterial activity. Nineteen structures against gram (+) bacteria had good antibacterial activity. Among these derivatives, five structures (4, 7, 8b, 9, and 10b) had significant activities with broad-spectrum, and structure 10b (with 27% yield) had the best result compared to other ones (Fig. 3 and Table 2). Structures 4 and 10b showed equipotent activity to ampicillin as a reference drug against S. aureus ATCC 6538, while structures 8b, 9, and 11 exhibited half the potency of ampicillin (Fig. 3 and Table 2). In the case of B. subtilis, structure 10b showed equipotent activity to gentamicin sulfate and ampicillin, while structures 4, 8b, 9, and 11 had half the potency of ampicillin (Fig. 3 and Table 2). In addition, structures 4, 8b, and 10b showed good activity compared to ampicillin and gentamicin sulfate against E. Coli. Also, structures 3, 7, and 9 displayed moderate activity against the same organism compared to gentamicin sulfate and ampicillin (Fig. 3 and Table 2) (Rostom et al., 2014)

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Fig. 3

Chemical structures of 3–7, 8a-b, 9, 10a-b, and 11 (Rostom et al., 2014)

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According to antifungal activity results, structures 5, 6, 7, 8a, 8b, 9, 10a, 10b, and 11 had significant growth inhibitory activity against C. Albicans compared to amphotericin B and clotrimazole as reference drugs (Fig. 3 and Table 2) (Rostom et al., 2014)

Prakash et al. synthesized twenty-seven structures containing thiazole scaffold. The antimicrobial activity of derivatives was tested against 4g-negative and positive bacteria and 2 fungal strains. (Table 3). Structures 16c and 17c displayed higher antibacterial activity compared to chloramphenicol as a reference drug, especially against Staphylococcus aureus (Fig. 4 and Table 3). In general, structures 12, 13b, 14a, 14b, 15, 16b, and 17b had moderate antibacterial activity, while structures 13a, 13c, 14c, 16a, and 17a showed good activity (Table 3 and Fig. 4) (Prakash et al., 2014)

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Fig. 4

Chemical structures 12, 13a-c, 14a-c, 15, 16a-c, and 17a-c (Prakash et al., 2014)

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Antifungal activity evaluations showed structures 17a and 17c had excellent activity, especially against A. niger greater than the reference drug (Table 3 and Fig. 4) (Prakash et al., 2014)

A novel series of derivatives containing thiazole were synthesized by Desai and co-workers. In this study, prepared twelve analogues and investigated their antimicrobial activities against 4 bacteria and 3 fungal strains. Structures 18a, 18b, and 18 h showed good antibacterial activity against S. pyogenes in comparison to chloramphenicol as a reference drug (Fig. 5 and Table 4). Whereas structures 18a and 18 g displayed good activity against S. Aureus (Fig. 5 and Table 4). Also, structures 18b and 18 h showed very good activity against S. aureus, E. coli, and P. Aeruginosa (Fig. 5 and Table 4). Whereas structures 18c and 18i had excellent activity against S. aureus and P. Aeruginosa (Fig. 5 and Table 4) (Desai et al., 2015)

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Fig. 5

Chemical structures 18a-i (Desai et al., 2015)

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According to antifungal studies, structure 18f showed the most potent activity against C. albicans MTCC 227 and A. niger MTCC 282 in comparison to ketoconazole as a reference drug (Fig. 5 and Table 4). Among all derivatives, structures 18d and 18e had good activity against A. clavatus. Moreover, structure 18e exhibited good activity against A. niger (Fig. 5 and Table 4) (Desai et al., 2015)

Basha and co-workers synthesized a series of aroyl-4-heteroaryl pyrazoles and pyrroles containing thiazole scaffold and evaluated their antimicrobial activity against 4g-negative and positive bacteria and 2 fungal strains (Fig. 6 and Table 5). Structures 20c, 20d, 20f, 21d, and 21f were active against all bacteria strains, especially Bacillus subtilis in comparison to chloramphenicol as a reference drug (Fig. 6 and Table 5). Whereas structures 20d and 20f showed marginally higher activity against all tested concentrations (12.5, 25, 50, and 100 μg/well) toward the reference drug (Table 4). Structures 20a, 21a, and 21c displayed moderate activity, while 20b, 20e, 21b, and 21e exhibited the least activity. In addition, derivatives 20 and 21 (aromatized structures) showed higher activity than derivatives 19 (non-aromatized structures) (Fig. 6 and Table 5) (Basha et al., 2015)

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Fig. 6

Chemical structures of 19a-b, 20a-f, and 21a-f (Basha et al., 2015)

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On the other hand, Structures 20c, 20d, and 20f displayed excellent antifungal activity toward ketoconazole as a reference drug against Aspergillus niger at 100 μg (Fig. 6 and Table 5). In the case of Aspergillus niger at 100 μg, structures 19a, 19b, 21b, and 21e demonstrated the least activity (Fig. 6 and Table 5) (Basha et al., 2015)

El-Kady et al. reported some structures containing thiazole scaffold and evaluated their antimicrobial activity against 2g-negative and positive and 1 fungal strain (Fig. 7 and Table 6). Among all derivatives, structures 22, 23a, 24a, and 25a had a wide spectrum of antimicrobial activity against Staphylococcus aureus NCINB 50080 and E. coli ATCC 1177 compared to ciprofloxacin as a reference drug, and structures 26, 27, 23b, 24b, 25b, and 25c effective against E. coli ATCC 1177 (Fig. 7 and Table 6). In addition, 28 and 29 were effective against Staphylococcus aureus NCINB 50080 (Fig. 7 and Table 6) (El-Kady et al., 2016)

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Fig. 7

Chemical structures of 22, 23a-b, 24a-b, 25a-c, 26, 27, 28, 29, and 30 (El-Kady et al., 2016)

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Antifungal activity evaluation showed structure 30 had remarkable activity toward AMB20 as a reference drug (Fig. 7 and Table 6) (El-Kady et al., 2016)

A series of ethyl 2-(2-(4-substituted)acetamido)-4-subtituted-thiazole-5-carboxylates (Fig. 8) were synthesized by Pawar and co-workers and their in vitro antimicrobial activities were tested against 3 bacteria (Table 7). In comparison, levofloxacin was used as a reference drug. The result of antibacterial activity revealed that structures 31a, 31b, 31c, 31d, and 32 had the most active and potent antimicrobial activity against B. subtilis, E. Coli, and S. aureus toward the reference drug (Fig. 8 and Table 7). Moreover, the same structures had potent antifungal activity against C. albicans, A. flavus, and A. niger as fungal strains which were chosen for the investigation of antifungal activity compared to miconazole and fluconazole as reference drugs (Fig. 8 and Table 7) (Pawar et al., 2016)

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Fig. 8

Chemical structures of 31a-d and 32 (Pawar et al., 2016)

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A novel series of 6-(5-Methyl-1H-1,2,3-triazol-4-yl)-5-[(2-(thiazol-2-yl)hydrazono)methyl]imidazo[2,1-b]thiazole derivatives (Fig. 9) were synthesized by Abdel-Wahab et al. All derivatives and vancomycine (As a reference drug) were tested against 6 bacteria and 2 fungal strains (Fig. 9). According to antibacterial studies, structure 33 exhibited significant antibacterial activity against all bacteria toward the reference drug. Whereas structures 34 and 35 demonstrated good activities against Staphelococcus aureus (Fig. 9). In addition, the same structures had good antifungal activities against Saccharomyces cervesia and Candida albicans NRRL Y-477 toward the reference drug (Fig. 9) (Abdel-Wahab et al., 2017)

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Fig. 9

Chemical structures of 33–35 and inhibition and MIC values of the structures 33–35 (Abdel-Wahab et al., 2017)

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Liao et al. synthesized a novel series of 2-substituted phenoxy-N-(4-substituted phenyl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-yl)acetamide derivatives (Fig. 10). All derivatives were tested against 2 bacteria and three fungal strains (Table 8). Bismerthiazol and hymexazol were used as antibacterial and antifungal reference drugs, respectively. Antibacterial studies showed four structures (36a, 36b, 36c, and 36d) had potent inhibition effects against Xoo and exhibited potent inhibition effects against Xac toward the reference drug (Fig. 10 and Table 8). In addition, EC₅₀ values of the same structures were good, which seem to be more potent than bismerthiazole. In addition, Structures 36b, 36c, and 36d (R₁ = OMe) had better activity compared to structures 36 h, 36i, and 36j (R₁ = 4-Cl) against xoo (Fig. 10 and Table 8). Whereas structures 36 h, 36i and 36j (R₁ = 4-Cl) had better activity compared to structures 36e, 36f and 36 g (3,4-di-Cl) (Fig. 10 and Table 8) (Liao et al., 2017)

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Fig. 10

Chemical structures 36a-j (Liao et al., 2017)

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According to antifungal activity studies, structure 36j displayed high activity against G. zeae toward the reference drug (Fig. 10 and Table 8) (Liao et al., 2017)

Shankerrao et al. synthesized a novel series of imidazothiazoles of benzofuran. The antimicrobial activities of structures were tested against 4 bacteria and 2 fungal strains with respect to ampicillin and flucanozole as antibacterial and antifungal reference drugs, respectively (Fig. 11 and Table 9). Among all derivatives, structures 37e and 37d displayed the best result against E. coli and S. Aureus (Fig. 11 and Table 9). In addition, structures 38b and 37a had moderate activity against E. coli and Klbesilla pneumona, while the same structures had an excellent effect against S. aureus and P. aeruginosa (Fig. 11 and Table 9) (Shankerrao et al., 2017)

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Fig. 11

Chemical structures of 37a-e and 38a-c (Shankerrao et al., 2017)

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According to antifungal activity studies, three structures (37a, 37b, and 38c) had excellent activity against A. niger and Trichoderma Virdae compared to other structures and the reference drug (Fig. 11 and Table 9). Whereas two structures (37c and 38a) had moderate activity against A. niger and Trichoderma Virdae (Fig. 11 and Table 9) (Shankerrao et al., 2017)

A novel series of 2-(benzo[d]thiazol-2-yl)phenyl-4-nitrophenyl alkyl/aryl substituted phosphoramidates were reported by Reddy et al. The derivatives were tested against 3 bacteria and 2 fungal strains in comparison to ampicillin and antibiotic as antimicrobial and antifungal reference drugs, respectively (Fig. 12 and Table 10). Among the derivatives, structures 39c, 39d, and 39 h had the best inhibition activity against Escherichia coli, Streptococcus aureus ATCC-25923, and Bacillus subtilis ATCC-1789 toward the reference drug (Fig. 12 and Table 10). In addition, structure 39e demonstrated good activity against Bacillus subtilis (Fig. 12 and Table 10) (Reddy et al., 2018)

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Fig. 12

Chemical structures 39a-h (Reddy et al., 2018)

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On the other hand, antifungal activity studies against 2 fungal strains at two concentrations, 50 and 100 μg/mL showed structures 39b, 39c, and 39 g had the best activity against C. albicans and A. niger at 100 µg/mL toward the reference drug (Fig. 12 and Table 10). In addition, structure 39a exhibited good activity against C. albicans and A. niger (Fig. 12 and Table 10). Whereas structures 39d and 39 h showed good activity against C. Albicans (Fig. 12 and Table 10). Moreover, structure 39f displayed good activity against A. niger (Fig. 12 and Table 10) (Reddy et al., 2018)

Ansari and Khan synthesized some of the structures containing thiazole scaffold. The derivatives were tested against 10g-negative and positive bacteria in comparison to ofloxacin as a reference drug. Structures 40a, 40c, and 40b had a higher activity with respect to other ones (Fig. 13 and Table 11). Structure 40c had the best activity against P. vulgaris, E. coli, and P. Aeruginosa (Fig. 13 and Table 11). Structure 40b had the highest activity against K. pneumonia and structure 40d displayed the highest activity against B. bronchiseptica. Moreover, structures 40a and 40b showed good activity against E. coli and P. Aeruginosa (Fig. 13 and Table 11) (Ansari and Khan, 2017)

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Fig. 13

Chemical structures 40a-d (Ansari and Khan, 2017)

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All 25 derivatives were tested against 5 fungal strains with respect to Ketoconazole as a reference drug. According to the results obtained, structures 40a and 40b had higher activity against Penicillium citrinum toward the reference drug (Fig. 13 and Table 11) (Ansari and Khan, 2017).

In 2019, a series of novel benzothiazole linked to acetohydrazide, carboxamide, and sulfonamide scaffolds (Fig. 14 and Table 12) were reported by Fadda and co-workers. Four bacteria were used in the antimicrobial activity evaluation (Table 12). Chloramphenicol and cephalothin were chosen as reference drugs. Structures 41a and 41b had broad-spectrum antibacterial activity against all organisms (Fig. 14 and Table 12). The same structures showed equipotent activity to chloramphenicol in inhibiting the growth B. subtilis. Whereas their activities were fifty percent lower than chloramphenicol against Bacillus thuringiensis. In the case of 45, 46, 47a-d, and 48, all structures showed good to moderate activity against gram-positive bacteria (Fig. 14. and Table 12). Structures 43 and 44 showed weak growth inhibitory with respect to the reference drugs against B. subtilis and B. Thuringiensis (Fig. 14 and Table 12). Structures 41a and 41b displayed good to moderate growth inhibitory against B. subtilis and B. thuringiensis toward the reference drugs (Fig. 14 and Table 12) (Fadda et al., 2019)

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Fig. 14

Chemical structures 41a-b, 42–46, 47a-d, and 48 (Fadda et al., 2019)

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According to antifungal activity studies, all derivatives were tested against F. oxysporum and B. fabae. Cycloheximide served as a reference drug. structures 41b and 42 exhibited moderate activity against B. fabae and F. Oxysporum (Fig. 14 and Table 12). Moreover, structure 41a had the best inhibition compared to other structures (Fig. 14 and Table 12) (Fadda et al., 2019)

Deshineni et al. synthesized a new series of ethyl-2-(3-((2-(4-(4-aryl)thiazol-2-yl)hydrazono)methyl)-4-hydroxy/isobutoxyphenyl)-4-methylthiazole-5 carboxylates by one-pot multi-component approach (Fig. 15). In this investigation, 4 bacteria and 2 fungal strains were used. Levofloxacin and miconazole were used as antibacterial and antifungal reference drugs. The result showed structures 49a, 49c, 50b, and 50c had a wide spectrum of antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Azatobacter with respect to the reference drug (Fig. 15 and Table 13). Further, Structures 49a and 50a displayed good activity against S. aureus, B. subtilis, E. coli, and Azatobacter (Fig. 15 and Table 13) (Deshineni et al., 2020)

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Fig. 15

Chemical structures 49a-c and 50a-c (Deshineni et al., 2020)

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Antifungal activity of all derivatives demonstrated structures 49b, 49c, 50b, and 50c had good activity against A.niger MTCC 282 and C. albicans MTCC 227 toward the reference drug (Fig. 15 and Table 13) (Deshineni et al., 2020)

Althagafi et al. synthesized a novel series of thiazole derivatives. As reference drugs, ampicillin and gentamicin were used. According to the results, structures 51, 53a, and 54 exhibited more potent activity against Staphylococcus aureus compared to ampicillin with preliminary antimicrobial activity values of 24.3 ± 0.63, 23.8 ± 0.72, and 24.1 ± 1.20 μg/ml, respectively (Fig. 16 and Table 14). Structures 55 and 56 displayed more potent activity against Salmonella typhimurium compared to gentamicin (Fig. 16 and Table 14) (Althagafi et al., 2019)

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Fig. 16

Chemical structures of 41–52, 53a-e, and 54–57 (Althagafi et al., 2019)

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Among all derivatives tested against two fungal strains, structures 51, 52, 53a, 53b, 53c, 53d, 53e, 54, and 57 exhibited higher activity against Aspergillus niger compared to amphotericin B as an antifungal reference drug (Fig. 16 and Table 14) (Althagafi et al., 2019)

A new series of N‑(4‑(4‑bromophenyl)thiazol‑2‑yl)‑2‑chloroacetamides were synthesized by Sharma and co-workers. The derivatives were tested against 3 bacteria and 2 fungal strains. As antibacterial and antifungal reference drugs, norfloxacin and fluconazole were used, respectively. Among the derivatives, structures 58, 59, and 60 had the best antimicrobial activity (Fig. 17). The antimicrobial activity results showed structure 60 had remarkable activity against S. Aureus (Fig. 17). Structure 58 had high activity against E. Coli and structure 59 had potent activity against B. Subtilis and E.coli (Fig. 17) (Sharma et al., 2019a)

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Fig. 17

Antimicrobial activity of the structures 58–60 (Sharma et al., 2019a)

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Antifungal activity results were found to structures 59 and 60 had high activity against 2 fungal strains (Fig. 17) (Sharma et al., 2019a)

A novel series of 4‑(4‑Bromophenyl)‑thiazol‑2-amines were synthesized by Sharma et al. All derivatives were tested against 3 bacteria and norfloxacin was used as a reference drug. Among all derivatives, structures 61, 62, 63, and 64 showed good antimicrobial activity toward the reference drug (Fig. 18). In vitro antimicrobial results showed structure 61 had good potential against E. Coli and S. Aureus (Fig. 18). Moreover, structure 63 had good potential against B. Subtilis (Fig. 18) (Sharma et al., 2019b)

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Fig. 18

Antimicrobial activity of the structures 61–64 (Sharma et al., 2019b)

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All derivatives were tested against 2 fungal strains in comparison to fluconazole as a reference drug. Antifungal activity results showed structure 64 had remarkable activity against C. Albicans and structure 62 had the highest potent against A. niger (Fig. 18) (Sharma et al., 2019b)

Sirakanyan et al. synthesized a novel series of derivatives containing thiazole scaffold which evaluated 11 derivatives against 6 bacteria with respect to ampicillin and streptomycin as reference drugs. Among all eleven derivatives synthesized, structures 65d, 65c, and 65f had lower activity against Pseudomonas aeruginosa toward streptomycin (Fig. 19 and Table 15). Structures 65f had lowes MIC against Bacillus cereus toward ampicillin (Fig. 19 and Table 15). Whereas structures 65b and 65c exhibited moderated activity against the same organism (Fig. 19 and Table 15). Structure 65f showed good activity against Listeria monocytogenes toward the reference drugs (Fig. 19 and Table 15) (Sirakanyan et al., 2021)

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Fig. 19

Chemical structures 65a-f (Sirakanyan et al., 2021)

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All derivatives tested against six fungal strains toward ketoconazole and bifonazole as reference drugs. according to the results, structures 65a, 65c, and 65e had high activity against Aspergillus versicolor compared to ketoconazole (Fig. 19 and Table 15). Moreover, structure 65a had significant activity against P. verrucosum var. Cyclopium and P. Funiculosum toward ketoconazole (Fig. 19 and Table 15) (Sirakanyan et al., 2021)

In 2020, a series of novel thiazolyl-1,2,3-triazolyl-alcohol derivatives synthesized by Jagadale et al. In this study, were used 2 bacteria. Streptomycin was used as a reference drug. Among all derivatives, structures 66b, 66f and 76i showed good antibacterial activity against S. albus toward the reference drug (Fig. 20 and Table 16) (Jagadale et al., 2020)

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Fig. 20

Chemical structures 66a-i (Jagadale et al., 2020)

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Antifungal activity studies which were tested against 4 fungal strains showed structures 66a, 66c, 66d, 66e, 66f, 66 g, 66 h, and 66i had remarkable activity against A. niger compared to ravuconazole as a reference drug (Fig. 20 and Table 16) (Jagadale et al., 2020)

Patel and co-workers reported 4-thiazolidinone fused pyrimidines. Ten derivatives were tested against 4 bacteria with respect to ciprofloxacin as a reference drug. Among all derivatives, structures 67c and 67d (2 and 3-CH₃) and 67a (3-NO₂ had good activity against P.aeruginosa MTCC 741 and E.coli MTCC 442 toward the reference drug (Fig. 21 and Table 17). In addition, structures 67b (2-Cl) and 67d (3-CH₃) showed good activity against S.aureus MTCC 96 and S.pyogenus MTCC 443 with respect to the reference drug (Fig. 21 and Table 17) (Patel et al., 2020)

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Fig. 21

Chemical structures 67a-e (Patel et al., 2020)

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All derivatives were tested against 3 fungal strains. In between, structures 67c, 67d, and 67e had low activity to some extent against C. Albicans (Fig. 21 and Table 17) (Patel et al., 2020)

Shinde et al. evaluated the antibacterial activity of a series of 2-(4-(benzo[d]thiazol-5-ylsulfonyl) piperazine-1-yl)-N-substituted acetamides against 4 bacteria with respect to ciprofloxacin as a reference drug. Among all derivatives, structures 68a, 68c, 68e, 68 g, and 68 k showed moderate activity against E.coli and P. aeruginosa toward the reference drug (Fig. 22 and Table 18). In addition, structures 68b, 68 h, 68i, 68d, and 68j displayed superior activity against S. aureus and B.subtilis toward the reference drug (Fig. 22 and Table 18) (Shinde et al., 2020)

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Fig. 22

Chemical structures 68a-k (Shinde et al., 2020)

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All derivatives and clotrimazole (As reference drug) were tested against Aspergillus fumigatus and C. Albicans and results showed structures 68b, 68f, 68 g, and 68j had good activity against C. Albicans (Fig. 22 and Table 18). Moreover, structure 68d had good activity against A. fumigatus (Fig. 22 and Table 18) (Shinde et al., 2020)

A series of novel bis(azolyl)sulfonamidoacetamides were synthesized by Sankar P et al. Chloramphenicol as a reference drug and all derivatives were tested against 4 bacteria. Among all derivatives, structures 72a, 72c, and 74c showed low minimal inhibitory concentrations (MICs) against Bacillus subtilis, equal to the reference drug (Fig. 23 and Table 19). In general, derivatives 71 and 72 demonstrated greater activity compared to derivatives 69, 70, 73, and 74 (Fig. 23). In addition, derivatives 73 and 74 exhibited more activity compared to derivatives 69 and 70 (Fig. 23) (Ss et al., 2021)

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Fig. 23

Chemical structures 69a-c-74a-c (Ss et al., 2021)

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All derivatives were tested against Aspergillus niger and Penicillium chrysogenum except 69a, 69b, 70a, and 70b (Fig. 23). Structures 72c and 74c had low MICs against Aspergillus niger, but had equal MICs compared to ketoconazole as a reference drug (Fig. 23). In general, derivatives 73 and 74 exhibited greater activity compared to derivatives 69, 70, 71, and 72 (Fig. 23). Whereas derivatives 71 and 72 displayed higher activity compared to 69 and 70 (Fig. 23) (Ss et al., 2021)

Khidre and Radini. evaluated the antibacterial activity of a novel series of structures containing thiazole scaffold against 4 bacteria with respect to ampicillin as a reference drug. Among all derivatives, structure 75 showed good antimicrobial activity against B. subtilis, S. aureus, P. aeruginosa, and E. coli toward the reference drug (Fig. 24 and Table 20). Moreover, structure 76 showed great activity against P. aeruginosa and E.coli (Fig. 24 and Table 20) (Khidre and Radini, 2021)

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Fig. 24

Chemical structures 75–76 (Khidre and Radini, 2021)

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Derivatives were tested against 2 fungal strains and as a reference drug, clotrimazole was used. According to the results, structure 75 exhibited the most activity against C. albicans and Aspergillus flavus toward the reference drug (Fig. 24 and Table 20). Generally, structure 75 had the best biological activity compared to other structures due to existing bromine at the para position of the phenyl ring (Fig. 24 and Table 20) (Khidre and Radini, 2021)

Shabaan et al. synthesized a novel series of 1,3,4-thiadiazines and 1,3-thiazoles derivatives. Some derivatives were tested against 2 bacterial and 2 fungal strains with respect to neomycin and cyclohexamide as antibacterial and antifungal reference drugs, respectively. Structures 77, 78b, 79a, 80, and 78a had lower MIC against S. aureus, while structures 81 and 82 showed higher MIC values (Fig. 25 and Table 21). In addition, structures 78a, 78b, and 77 demonstrated moderate activity against E. Coli, while structures 80 and 79a exhibited higher MIC values (Fig. 25 and Table 21). Structures 81 and 82 had higher MIC and MBC values against S. aureus and E. Coli (Fig. 25 and Table 21). Moreover, structures 78a showed the most potent activity against S. aureus and E. Coli toward the reference drug (Fig. 25 and Table 21). Structure 77 displayed significant activity against S. aureus, Whereas two structures (78b and 79b) exhibited moderate activity (Fig. 25 and Table 21). Also, structures 79a, 82, and 81 had low activities against S. aureus (Fig. 25 and Table 21). In contrast, Structures 83 and 84 displayed no activity against S. aureus (Fig. 25). Structures 81 had potent activity against E. coli, while structures 82, 77, 80, and 79b showed low activities toward the reference drug (Fig. 25 and Table 21) (Shabaan et al., 2021)

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Fig. 25

Chemical structures 77–84 (Shabaan et al., 2021)

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On the other hand, five structures (78b, 81, 77, 80, and 79b) displayed remarkable activity against A. niger toward the reference drug (Fig. 25 and Table 21). Whereas structures 82, 83, and 79a displayed moderately active against A. niger (Fig. 25 and Table 21). Structures 78b and 77 had remarkable activities against C. albicans (Fig. 25 and Table 21). Whereas two structures (82 and 79b) displayed moderate activity (Shabaan et al., 2021)

A new series of 4-(6-substituted quinolin-4-yl)-Narylthiazol-2-amines were synthesized by Thakare et al. All derivatives were tested against 4 bacteria. As a reference drug, streptomycin was used. Structure 85f had moderated activity against E. Coli (Fig. 26 and Table 22). Furthermore, structures 85a, 85e, 85f, and 85 g displayed moderate activity against S. albus, while structures 85b and 85d had good activity (Fig. 26 and Table 22) (Thakare et al., 2021)

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Fig. 26

Chemical structures 85a-n and 86a-b (Thakare et al., 2021)

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The antifungal activities of derivatives were evaluated against 2 fungal strains with respect to ravuconazole and fluconazole as the reference drugs. According to the results, structures 85 h, 85i, 85j, 85 k, 85 l, 85 m, 85n, 86a and 86b were found to have moderate to good activity against A. niger toward ravuconazole (Fig. 26 and Table 22). Moreover, structure 86a showed good activity against A. candida and comparable activity against A. niger (Fig. 26 and Table 22). Structure 85b showed moderate activity against A. candida (Fig. 26 and Table 22). The structure 85c had good activity against A. candida and A. niger (Fig. 26 and Table 22) (Thakare et al., 2021)

In 2022, El-Hagrassey and co-workers synthesized a novel series of derivatives containing thiazole. Ampicillin as a reference drug and the novel derivatives were tested against 4 bacteria. According to antibacterial activity studies, structure 90 displayed the highest activity against both gram-negative and positive bacteria, Whereas structure 89 had a weak effect on E. coli and P. Aeruginosa (Fig. 27 and Table 23). Also, structures 87a, 87b, 87c, and 88 did not show an effect on E. coli and structures 87a, 87b, and 88 had no effect on S.aureus (Fig. 27). Structures 87b and 88 did not show effect on P. aeruginosa and B. Subtilis (Fig. 27) (El-Hagrassey et al., 2022)

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Fig. 27

Chemical structure 87a-c and 88–90 (El-Hagrassey et al., 2022)

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On the other hand, derivatives were tested against C. Albicans for investigation of antifungal activity. As a reference drug, clotrimazole was used. Structure 90 had the highest activity against C. albicans (Fig. 27 and Table 23). In addition, structures 87b and 88 had no effect on C. albicans (Fig. 27). Whereas structure 89 showed good activity against C. albicans (Fig. 27 and Table 23) (El-Hagrassey et al., 2022)

A novel series of 2,3-Dihydropyrido[2,3-d]pyrimidine-4-ones and Pyrrolo[2,1-b][1,3]benzothiazoles synthesized by Al-Mutairi et al. Cefotaxime as reference drug and all derivatives were tested against 6 bacteria (Fig. 28 and Table 13). The antibacterial evaluations of all derivatives exhibited 4 structures (91a, 91b, 92a, and 92d) that had higher activity toward the reference drug (Fig. 28 and Table 13). Structure 91a had an equipotent activity with respect to the reference drug against Chlamydia pneumonia and Bacillus subtilis, and structure 92a had equipotent activity against Chlamydia pneumonia and Bacillus subtilis, while had more activity against Staphylococcus aureus (Fig. 28 and Table 13). Moreover, structure 92d because of the presence of pyrrolobenzothiazole with p-fluorophenyl substituent exhibited significant activity against all bacteria compared to the reference drug (Fig. 28 and Table 13). In general, structures 92b, 92c, and 92e had good inhibition activity against all bacterial strains (Fig. 28 and Table 13) (Al-Mutairi et al., 2022)

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Fig. 28

Chemical structures 91a-b and 92a-e (Al-Mutairi et al., 2022)

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All derivatives were tested against 3 fungal strains. As a reference drug, fluconazole was used for the investigation of antifungal activity. According to studies, structures 91a, 91b, 92a, and 92d had high activity (Fig. 28 and Table 24). Structure 92d showed equipotent activity against Aspergillus flavus while had more high activity against Ganoderma lucidum and Candida albicans toward the reference drug (Fig. 28 and Table 24). Structure 92a showed significant activity against Ganoderma lucidum and Aspergillus flavus and had more potent activity against Candida albicans compared to the reference drug (Fig. 28 and Table 24). Also, structures 91a and 91b had good activity against Aspergillus Flavus, Candida Albicans, and Ganoderma Lucidum (Fig. 28 and Table 24) (Al-Mutairi et al., 2022)

Othman et al. synthesized and investigated the antimicrobial activity of a series of thiazole, thiophene, and thieno[2,3-d]pyrimidines against 4 bacteria and 2 fungal strains. As antibacterial and antifungal reference drugs, ampicillin and clotrimazole were used, respectively. Structure 93 against S. aureus and B. Subtilis had potent activity (Fig. 29 and Table 25). Structures 94, 95, and 96 showed weak sensitivity against P. aeruginosa and E. Coli (Fig. 29 and Table 25). In addition, structures 98 and 99 against P. aeruginosa exhibited moderate potency, while structures 97 and 93 had potent activity (Fig. 29 and Table 25). Moreover, structures 98 and 97 displayed less sensitivity against E. coli toward the reference drug (Fig. 29 and Table 25) (Othman et al., 2022)

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Fig. 29

Chemical structures 93–99 (Othman et al., 2022)

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Four structures (98, 99, 96, and 93) against A. fumigatus RCMB showed potent antifungal activity. Further, structures 95 and 93 showed remarkable antifungal activity against C. albicans toward the reference drug (Fig. 29 and Table 25) (Othman et al., 2022)

A novel series of structures containing thiazole scaffold were synthesized by Kartsev and co-workers and evaluated their antibacterial activity against 6 bacteria, using a microdilution method. As reference drugs, Streptomycin and ampicillin were used. Structure 100a displayed the best activity against E. coli with respect to the reference drugs (Fig. 30 and Table 26). Structure 101 exhibited good activity against B. cereus and S. typhimurium (Fig. 30 and Table 26). Also, structure 102 exhibited good activity against S. typhimurium (Fig. 30 and Table 26). In addition, structures 103b, 102, and 100a exhibited higher potential than ampicillin against E. coli, methicillin resistant Staphylococcus aureus, and P. aeruginosa (Fig. 30 and Table 26) (Kartsev et al., 2022)

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Fig. 30

The structures of heteroaryl (aryl) thiazole derivatives 100a-d, 101–102, and 103a-c (Kartsev et al., 2022)

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The antifungal activity of derivatives was evaluated against 6 fungal strains. As reference drugs, bifonazole and ketoconazole were used. Structure 103b displayed the best activity, while structure 100b showed the lowest activity (Fig. 30 and Table 26). Structures 103b and 101 against T. viride showed excellent activity nearly 29 times better compared to ketoconazole and four times better than bifonazole as well as against P. cyclpoium var. verucosum, P. funiculosum, A. versicolor, and A. niger (Fig. 30 and Table 26). Structures 103c and 102 against T. viride showed good activity, followed by structures 103a, 100c, and 100d (Fig. 30 and Table 26). All derivatives demonstrated better activity against T. viride than ketoconazole, while structures 100a and 100b had not a good activity. In general, most of the derivatives had more potent activity against all fungi toward ketoconazole, except for P. cyclpoium var. Verucosum which only structures 103c, 103b, and 101 were more active than ketoconazole (Fig. 30 and Table 26) (Kartsev et al., 2022)

A series of coumarin thiazoles were synthesized by Yang et al and their antimicrobial activities were evaluated against 9 bacteria. As antibacterial reference drugs, norfloxacin and ciprofloxacin were used. Structure 104d against S. aureus displayed equivalent antibacterial activity toward norfloxacin (Fig. 31 and Table 27). Structures 104a-b against E. coli ATCC 25922 showed the same MIC with respect to norfloxacin (Fig. 31 and Table 27). Structures 104b and 104c against most tested strains showed poor bioactivities (Fig. 31). In addition, structures 109b-d exhibited 2 to 8 times antibacterial potency against MRSA toward the reference drugs (Fig. 31 and Table 27). Structure 109a against E. coli ATCC 25,922 showed almost 2 times inhibition potency toward norfloxacin (Fig. 31 and Table 27). Structure 109c against A. baumanii showed high activity with respect to ciprofloxacin with the same MIC value and 8-fold more active than norfloxacin (Fig. 31 and Table 27). In the case of 107a-g, structure 107a against MRSA, Enterococcus faecalis, and Staphylococcus aureus showed the best antibacterial efficacy (Fig. 31 and Table 27). The same structure against MRSA was 8 times superior to ciprofloxacin and norfloxacin (Fig. 31 and Table 27). Structure 107b against MRSA, S. aureus, A. baumannii, and E. faecalis showed good activity which was 4 times higher than or equivalent to norfloxacin (Fig. 31 and Table 27). Structures 107c-g exhibited no bioactivity or remarkably declined inhibitory activity (Fig. 31). Further, structures 104 and 106a showed no sensitivity to the tested germs, while structure 108b showed 2-fold bacteriostatic activity toward ciprofloxacin and norfloxacin against MRSA (Fig. 31 and Table 27) (Yang et al., 2022)

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Fig. 31

Chemical structures 104a-d, 105a-b, 106, 107a-g, 108a-b, and 109a-d (Yang et al., 2022)

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Antifungal activity was evaluated against 5 fungal strains. As an antifungal reference drug, fluconazole was used. Structure 107a against C. tropicalis, A. fumigatus, C. albicans ATCC 90023, and C. parapsilosis ATCC 22019 showed the best activity toward the reference drug, while structures 105a, 106, and 107b-c had weak activity against all fungi (Fig. 31). In addition, structures 105b, 107d-g, and 106a–b against C. albicans ATCC 90023 demonstrated moderate to good antifungal activity (Fig. 31 and Table 27). Structure 107a against all tested fungi except C. albicans showed promising antifungal potential and was selected as a potential drug candidate (Fig. 31 and Table 27) (Yang et al., 2022)

3 Thiazole derivatives with anti-inflammatory activity

The response to diverse stimuli by organisms is meaning Inflammation. There are a lot of diseases like asthma, psoriasis, and arthritis that deal with inflammation. Therefore, the need for anti-inflammatory drugs is needed more than ever. Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most important types of anti-inflammatory drugs., but their long-term use shows remarkable side effects such as nephrotoxicity and adverse cardiovascular events (Petrou et al., 2021)

Deb et al. evaluated in vivo anti-inflammatory activity of a new series of N-(benzo[d]thiazol-2-yl)-2-(substituted)acetamide derivatives and 2-substituted-N-(1,3-thiazole-2-yl)acetamide derivatives, using the carrageenan-induced rat paw edema model. According to the results, four structures (110a-d) were found to have significant activity with respect to other structures (about 84–93 % of the reference) (Fig. 32 and Table 28). Moreover, structures 110d and 110c with 4-methoxyaniline and 4-fluoroaniline substituent exhibited good activity toward structures 110b and 110a with imidazole and triazole scaffold (Fig. 32 and Table 28) (Deb et al., 2014)

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Fig. 32

Chemical structures 110a-d (Deb et al., 2014)

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A novel series of 1,2,3,4-tetrahydronaphthalen-6-yl-thiazoles and thiazolidinones were synthesized by Haiba and co-workers, but Twenty four structures were chosen for analgesic and anti-inflammatory activity. Anti-inflammatory activity study showed structures 114 and 118 had equipotent activity toward indomethacin as a reference drug with quicker action onset. In addition, six structures (111a, 111b, 113, 117, 119b, and 119c) showed dual analgesic and anti-inflammatory (Fig. 33). Among all derivatives, structure 113 (carrying coumarin-thiazole ring) in comparison with indomethacin exhibited remarkable dual analgesic and anti-inflammatory activity (Fig. 33 and Table 29). According to anti-inflammatory activity at 4 h, eleven structures (113, 118, 114, 111b, 119b, 111c, 112, 115, 116, 117, and 119a) showed the greatest anti-inflammatory potency (Fig. 33 and Table 29). Remarkable edema inhibition at the 1st h post-administration was observed by four structures (112, 114, 113, 118) (Fig. 33 and Table 29) (Haiba et al., 2014)

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Fig. 33

The structures of 1,2,3,4-tetrahydronaphthalen-6-yl-thiazole and thiazolidinone derivatives (111a-c, 112–118, and 119a-c) (Haiba et al., 2014)

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In 2015, Khloya et al. evaluated the anti-inflammatory activity of a series of pyrazolylthiazole carboxylates and corresponding acid derivatives. Evaluation of thirty-two derivatives showed structure 120 h had the best activity and structures 121b, and 121i had remarkable anti-inflammatory activity after 3 h (Fig. 34 and Table 30). After three hours of carrageenan injection, eight structures (120a, 120c, 120f, and 121a-e) exhibited remarkable activity (Fig. 34 and Table 30). Nine structures (120d-e, 120 g–h, 121b, 121e–f, 121 h, and 121 g) were found to have significant activity compared to the reference drug after 4 h of carrageenan injection (Fig. 34 and Table 30). In general, the ester derivatives were better than the acids and the results after 4 h of carrageenan injection revealed that all derivatives do not get simply metabolized in the body (Fig. 34 and Table 30) (Khloya et al., 2015)

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Fig. 34

The structures of pyrazolylthiazole carboxylates (120a-h) and corresponding acid derivatives (121a–i) (Khloya et al., 2015)

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A novel series of structures thiazole bearing pyrazole were synthesized via a one-pot reaction method by D. Kamble and co-workers. According to in vivo anti-inflammatory activity results, structures 122d and 122e had stronger protection against inflammation by Carrageenan at 180 min, while at 90 min onwards structure 122e showed outstanding protection against inflammation (Fig. 35 and Table 31). In addition, structure 122e at 30, 90, 120, and 150 min exhibited unremarkable differences with respect to diclofenac as a reference drug (Fig. 35 and Table 31). Four structures (122a, 122b, 122c, and 122f) showed considerable differences compared to the control, while its anti-inflammatory activity at 30, 60, and 90 min had non-significant differences compared to the reference drug (Fig. 35 and Table 31). Moreover, structures 122c, 122e, and 120f had strong COX-II inhibitory activity (Fig. 35) (Kamble et al., 2016)

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Fig. 35

Chemical structures 122a-f (Kamble et al., 2016)

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Kumar et al. reported N-[2-(1H-indol-3-yl)ethyl]-2amino/aminoaryl/alkyl/aryl/heteroarylthiazole-4-carboxamides. The anti-inflammatory activity of all derivatives were evaluated. Among all derivatives, structures 123b (p-tolyl), 123d (2-thienyl), 124a (NH₂), and 124c (p-fluoro aminophenyl) displayed significant anti-inflammatory activity at 1 h compared to indomethacin as reference drug (Fig. 36 and Table 32). After 4 h, three structures (123b, 124a, and 124b) stayed active (Fig. 36 and Table 32). Also, five structures (123a, 123c, 123e, 124b, and 124d) showed good activity after 1 h (Fig. 36 and Table 32) (Kumar et al., 2016)

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Fig. 36

Chemical structures 123a-e and 124a-d (Kumar et al., 2016)

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In 2017, a new series of structures containing thiazoles were synthesized by Toma et al. The mentioned derivatives were investigated for their anti-inflammatory activity. Among all derivatives, structures 126b, 126c, and 126d displayed good activity after 1 and 2 h compared to diclofenac as a reference (Fig. 37 and Table 33). Structures 125a, 125b, and 126a showed moderate activity after 1, 2, and 3 h (Fig. 37 and Table 33). In general, it seems that the 4-pyridyl substituent and the carboxylate ester group are effective in anti-inflammatory activity (Fig. 37 and Table 33) (Toma et al., 2017)

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Fig. 37

Chemical structures 125a-b and 126a-d (Toma et al., 2017)

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Abdelazeem and co-workers evaluated the in vivo anti-inflammatory activity of a series of diphenylthiazole derivatives. According to the stated results, structure 127 had the best activity that was comparable with indomethacin as a reference drug after 1, 3, and 5 h (Fig. 38 and Table 34). Also, structure 128 showed excellent activity compared to the reference drug after 1 h (Fig. 38 and Table 34) (Abdelazeem et al., 2017)

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Fig. 38

Chemical structures 127–128 (Abdelazeem et al., 2017)

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Wang et al. evaluated the anti-inflammatory activity of a new series of new benzo[d]thiazole-hydrazones. Anti-inflammatory activity results demonstrated ten structures (129a, 129b, 129c, 129d, 129e, 129f, 129 g, 129 h, 129i, and 129j) had greater activity (Fig. 39 and Table 35). Moreover, structures 129f and 129 h exhibited the highest docking scores (Fig. 39 and Table 35) (Wang et al., 2017)

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Fig. 39

Chemical structure 129a-j (Wang et al., 2017)

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Mohareb et al. evaluated the anti-inflammatory activity of new structures of fused thiazole derivatives derived from 2-(2-oxo-2H-chromen-3-yl)thiazol-4(5H)-one (Fig. 40 and Table 36). The evaluation of anti-inflammatory activity showed structures 133, 134b, 136, 137a and 137b compared to other derivatives at 3 graded doses had high activity (Fig. 40 and Table 36). Structures 130a-c, 131a-c, 132, 133, 134a, 135, 137a, and 137b demonstrated the high antiulcer activity (Fig. 40 and Table 36) (Mohareb et al., 2017)

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Fig. 40

Chemical structures 130a-c, 131a-c, 132–133, 134a-b, 135–136, and 137a-b (Mohareb et al., 2017)

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Abu-Hashem et al. synthesized thiazolopyrimidines, 1,3,5-oxadiazepines, 1,3,5-triazines, and benzodifuranyl derivatives. Among all derivatives containing thiazole scaffold, ten structures (138a–f, 139a–b, and 140a–b) exhibited the highest anti-inflammatory activity compared to diclofenac as a reference drug after 3 h (Fig. 41 and Table 37) (Abu-Hashem et al., 2020)

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Fig. 41

Chemical structures 138a-f, 139a-b, and 140a-b (Abu-Hashem et al., 2020)

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Kamat and co-workers evaluated the anti-inflammatory activity of a series of pyridine- and thiazole-based hydrazides, using denaturation of the bovine serum albumin method. Among all derivatives, three structures (141f, 141 g, and 141 h) showed good activity toward other structures (Fig. 42 and Table 38). The highest inhibition among all derivatives was achieved for structure 141 h at 5 different concentrations (Fig. 42 and Table 38). In addition, structures 141a, 141b, 141c, 141d, and 141e had moderate inhibition (Fig. 42 and Table 38) (Kamat et al., 2020)

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Fig. 42

Chemical structures 141a-h (Kamat et al., 2020)

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Maghraby et al. reported and evaluated the anti-inflammatory activity of a series of structures containing thiazole scaffold. According to in vivo anti-inflammatory activity results, three structures (142, 143, and 144) showed significant activity (Fig. 43 and Table 39). Further, structure 144 showed the highest inhibition toward other structures compared to the reference drug after 4 h (Fig. 43 and Table 39) (Maghraby et al., 2020)

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Fig. 43

Chemical structures of 142–144 (Maghraby et al., 2020)

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Han et al. evaluated the anti-inflammatory activity of a series of new 2-aminobenzo[d]thiazole derivatives, using the carrageenan-induced mouse paw edema method. The results of the study showed structures 145, 146, and 147 had the best activity compared to other structures and the same structures showed as potent sEH inhibitors, but structure 147in rat liver microsomes was unstable (Fig. 44 and Table 40) (Han et al., 2021)

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Fig. 44

Chemical structures of 143–145 (Han et al., 2021)

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Ankali et al. evaluated the anti-inflammatory activity of a novel series of 1,3-Thiazoles. According to the results, four structures (148a, 148b, 148c, and 148d) exhibited more potent anti-inflammatory activity with Cl, NO₂, and Br substituting on the phenyl ring compared to diclofenac as reference drugs (Fig. 45 and Table 41). Moreover, structures 148e and 148f with CH₃ and OH substitutes showed moderate activity compared to structures 148a, 148b, and 148d after 5 h (Fig. 45 and Table 41). It seems that structures with electron-withdrawing groups such as Cl and NO₂ on the phenyl ring are greater anti-inflammatory activity toward structures with electron-donating groups (Ankali et al., 2021)

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Fig. 45

The structures of 1,3-thiazole derivatives(148a-f) (Ankali et al., 2021)

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In 2021, a series of thiazole/oxazole substituted benzothiazole derivatives were synthesized by Kumar and Singh. All derivatives were tested against carrageenin at 3 different doses for their anti-inflammatory activity. According to the results, structure 149 with ethyl group at the 3-position of benzothiazole displayed greater activity compared to phenyl butazon as a reference drug (Fig. 46 and Table 42). In addition, derivatives 150a-h showed moderate anti-inflammatory activity (Fig. 46 and Table 42). Among the derivatives, structure 150e with chlorine at the 4-position of the phenyl azo group exhibited remarkable anti-inflammatory activity (Fig. 46 and Table 42) (Kumar and Singh, 2021)

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Fig. 46

Chemical structures 149 and 150a-h (Kumar and Singh, 2021)

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In 2022, Sukanya et al investigated the inhibition of novel series of thiazole derivatives against two enzymes. The investigation of anti-inflammatory activity exhibited structures 151a and 151b had significant activity compared to other structures (Fig. 47 and Table 43). The same structures had moderated activity against MMP-9 compared to positive control and had remarkable activity against MMP-2 compared to positive control (Fig. 47 and Table 43). It seems that the presence of NO₂ substitute at both phenyls is effective in their anti-inflammatory activity (Sukanya et al., 2022)

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Fig. 47

Chemical structures 151a-b (Sukanya et al., 2022)

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Saliyeva and co-workers synthesized a series of derivatives containing thiazole scaffold and evaluated in vivo anti-inflammatory activity in white rats carrageenan-induced edema paw model. Diclofenac sodium was used as a reference drug. All derivatives showed moderate anti-inflammatory activity (Fig. 48 and Table 44). Structures 152a and 152b displayed the best activity compared to the reference drug (Fig. 48 and Table 44). Moreover, structures 152c, 152d, 152e, 152f, 152 g and 152 h exhibited moderate to good activity (Fig. 48 and Table 44) (Saliyeva et al., 2021)

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Fig. 48

Chemical structures 152a-h (Saliyeva et al., 2021)

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