Synthesis, characterization and antimicrobial evaluation of 2,5-disubstituted-4-thiazolidinone derivatives

Aakash Deep; Sandeep Jain; Prabodh Chander Sharma; Sanjeev K. Mittal; Priyanka Phogat; Manav Malhotra

doi:10.1016/j.arabjc.2010.10.032

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Original article

7 (

); 287-291

doi:

10.1016/j.arabjc.2010.10.032

Synthesis, characterization and antimicrobial evaluation of 2,5-disubstituted-4-thiazolidinone derivatives

Aakash Deep^a,*, Sandeep Jain^b, Prabodh Chander Sharma^c, Sanjeev K. Mittal^d, Priyanka Phogat^e, Manav Malhotra^f

a Department of Pharmaceutical Sciences, G.V.M. College of Pharmacy, Sonepat 131 001, India

b Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar 125 001, India

c Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra 136 118, India

d Department of Pharmaceutical Sciences, S.D. College of Pharmacy, Barnala 148 101, India

e Department of Pharmaceutical Sciences, Hindu College of Pharmacy, Sonepat 131 001, India

f Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Ferozpur Road, Moga 142 001, India

*Corresponding author. Mobile: +91 9896096727 aakashdeep82@gmail.com (Aakash Deep)

Received: 2010-10-8, Accepted: 2010-10-29, Published: 2010-07-01

Disclaimer:
This article was originally published by Elsevier and was migrated to Scientific Scholar after the change of Publisher.

Available online 9 November 2010

Peer review under responsibility of King Saud University.

Abstract

In the present study novel derivatives of 4-thiazolidinone were prepared from biphenyl-4-carboxylic acid and evaluated for their in vitro antimicrobial activity against two Gram negative strains (Escherichia coli and Pseudomonas aeruginosa) and two Gram positive strains (Bacillus subtilis and Staphylococcus aureus) and fungal strain Candida albicans and Aspergillus niger. The newly synthesized compounds were characterized by IR, ¹H NMR and C, H, N analyses. The results revealed that all synthesized compounds have a significant biological activity against the tested microorganisms. Among the synthesized derivatives 4g (biphenyl-4-carboxylic acid [2-(3-bromophenyl)-5-(3-nitrobenzylidene)-4-oxo-thiazolidin-3-yl]-amide) and 4i (biphenyl-4-carboxylic acid [5-(3-bromobenzylidene)-2-(3-bromophenyl)-4-oxo-thiazolidin-3-yl]-amide) were found to be most effective antimicrobial compounds.

Keywords

Hydrazones

4-Thiazolidinone

Antibacterial and antifungal activity

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1 Introduction

Microbial resistance to antimicrobial agents is of grave concern in the medical community. Hence, the development of novel, potent, and unique antimicrobial agents are the preeminent way to overcome microbial resistance and develop effective therapies. 4-Thiazolidinone and its derivatives have attracted considerable attention for the past few decades due to their chemotherapeutical values (Verma and Saraf, 2008). These derivatives are known to possess several promising pharmacological actions such as antimicrobial (Bondock et al., 2007; Shah and Desai, 2007; Samir et al., 2007; Vicini et al., 2006; Sharma et al., 2006; Handan et al., 2005 ), analgesic (Knutsen et al., 2007), anti-inflammatory (Ottana et al., 2005; Goel et al., 1999), anti-HIV (Balzarini et al., 2007), cytotoxic (Mujeebur et al., 2005), and anticonvulsant (Gursoy and Terzioglu, 2005) activities. Also, 4-thiazolidinones have been found as novel inhibitors of bacterial enzyme MurB, a key enzyme responsible for the synthesis of peptidoglycon (Andres et al., 2000).

Inspired by the above facts and in continuation of our ongoing research program in the field of synthesis and antimicrobial activity of medicinally important compounds (Deep et al., 2010b; Madhukar et al., 2009; Kumar et al., 2010 ), we hereby report the synthesis and antimicrobial activity of 4-thiazolidinone derivatives. All these compounds have been reported with their anti-inflammatory activity elsewhere (Deep et al., 2010a). The structures of all compounds have been confirmed by elemental and spectral analysis (IR and ¹H NMR).

2 Experimental

The purity of the synthesized compounds were ascertained by thin layer chromatography on silica gel G in various solvent systems using iodine vapours as detecting agent. Melting points were determined by the melting point determination apparatus (TEMPO) in open capillary tubes and are uncorrected. Elemental analyses were done using Carlo Erba 1106 CHN Analyzer. Infra-red spectra were recorded on Perkin Elmer Spectrum RXI FTIR spectrophotomer in KBr phase. Proton NMR spectra were recorded on Bruker Avance II 400 NMR Ultra Shield Spectrometer using DMSO-d₆ as a solvent and tetramethyl silane as internal standard. Chemical shift value is expressed in delta parts per million (δ ppm). All the compounds have been screened in vivo for their anti-inflammatory activity.

2.1

2.1 Chemistry

A series of biphenyl-4-carboxylic acid-5-(arylidene)-2-(aryl)-4-oxothiazolidin-3-yl-amides has been synthesized. Reaction of acid hydrazide (1) with aromatic aldehydes yielded the corresponding hydrazones (2a–c) which on further reaction with thioglycolic acid in methanol afforded the corresponding 2-substituted-4-thiazolidinones (3a–c). The compounds (3a–c) were further reacted with aromatic aldehydes in presence of few drops of glacial acetic acid to yield the 2,5-disubstituted-4-thiazolidinones (4a–l). The synthesized 2,5-disubstituted-4-thiazolidinones were characterized on the basis of the spectral and analytical studies.

2.2

2.2 General method

The title compounds were prepared in following steps:

2.2.1

2.2.1 Synthesis of hydrazone (2)

A mixture of biphenyl-4-carboxylic acid hydrazide (0.025 mol, 5.3 g) and required aromatic aldehydes (0.025 mol) was refluxed in methanol (50 ml) in the presence of a catalytic amount of glacial acetic acid for about 2 h. The mixture was cooled and the solid obtained was separated by filtration and recrystallized from methanol to give the corresponding hydrazones.

2.2.2

2.2.2 Synthesis of 2-substituted-4-thiazolidinone (3a–c)

A mixture of appropriate Schiff’s base (0.015 mol) (2) and required amount of thioglycolic acid (0.015 mol, 1.40 ml) in N,N-dimethylformamide (DMF) (50 ml), containing a pinch of anhydrous ZnCl₂ was refluxed for about 6 h. The reaction mixture was cooled and poured on to crushed ice. The solid thus obtained was filtered, washed with water and the product was recrystallized from rectified spirit.

2.2.3

2.2.3 Synthesis of 2,5-disubstituted-4-thiazolidinone (4a–l)

A suspension of 2-substituted-4-thiazolidinone (0.01 mol), required aromatic aldehydes (0.01 mol) and anhydrous sodium acetate was prepared in glacial acetic acid and refluxed for 5–7 h. After cooling, the solution was poured on crushed ice to precipitate the product. The product was recrystallized from ethanol.

By adopting similar type of procedures, and employing equimolar quantities of reactants, 12 compounds were synthesized. Physical and analytical data of synthesized compounds is given in Table 1. Synthetic pathway for preparation of title compounds is shown in Scheme 1.

Table 1 Physical data of 2,5-disubstituted-4-thiazolidinones.

Compound	Ar	Ar′	Molecular formula	Molecular weight	Melting point (°C)	Yield (%)	R_f value
4a	$C_{6} H_{5^{-}}$	$C_{6} H_{5^{-}}$	C₂₉H₂₂N₂O₂S	462.56	214–216	71.32	0.63
4b	$C_{6} H_{5^{-}}$	3-NO₂C₆H₄	C₂₉H₂₁N₃O₄S	507.56	217–219	78.14	0.71
4c	$C_{6} H_{5^{-}}$	4-ClC₆H₄	C₂₉H₂₁ClN₂O₂S	497.01	223–224	82.26	0.59
4d	$C_{6} H_{5^{-}}$	3-BrC₆H₄	C₂₉H₂₁BrN₂O₂S	541.46	216–217	79.40	0.62
4e	$C_{6} H_{5^{-}}$	4-OCH₃C₆H₄	C₃₀H₂₄N₂O₃S	492.59	210–212	81.60	0.68
4f	3-BrC₆H₄	$C_{6} H_{5^{-}}$	C₂₉H₂₁BrN₂O₂S	541.46	228–230	78.46	0.92
4g	3-BrC₆H₄	3-NO₂C₆H₄	C₂₉H₂₀BrN₃O₄S	586.46	238–239	78.40	0.88
4h	3-BrC₆H₄	4-ClC₆H₄	C₂₉H₂₀BrClN₂O₂S	575.90	225–227	81.20	0.79
4i	3-BrC₆H₄	3-BrC₆H₄	C₂₉H₂₀Br₂N₂O₂S	620.35	245–248	78.62	0.82
4j	3-BrC₆H₄	4-OCH₃C₆H₄	C₃₀H₂₃BrN₂O₃S	571.48	234–235	81.80	0.73
4k	4-FC₆H₄	$C_{6} H_{5^{-}}$	C₂₉H₂₁FN₂O₂S	480.55	242–243	79.34	0.78
4l	4-FC₆H₄	3-NO₂C₆H₄	C₂₉H₂₀FN₃O₄S	525.55	235–237	78.86	0.84

For mobile phase: chloroform:benzene:glacial acetic acid (3:1:1, v/v/v).

Preparation of biphenyl-4-carboxylic acid-5-(arylidene)-2-(aryl)-4-oxo-thiazolidin-3-yl-amides (4a–l).

2.3

2.3 Spectral data

2.3.1

2.3.1 Biphenyl-4-carboxylic acid (5-benzylidene-4-oxo-2-phenylthiazolidin-3yl)-amide (4a)

IR (KBr, cm⁻¹): 3198 (N–H), 3028–2923 (C–H), 1634–1657 (C⚌O), 1605–1483 (C⚌C), 1446–1402 (C–N). ¹H NMR (300 MHz, DMSO-d₆, δ ppm): 8.43–7.38 (m, 9H, Ar H), 8.06 (s, 1H, –NH), 7.68–7.50 (m, 5H, Ar′ H), 7.48–7.40 (m, 4H, Ar H), 7.32 (s, 1H, C⚌CH), 4.62 (s, 1H, –NCHS). Anal. Calcd. for C₂₉H₂₂N₂O₂S: C, 75.30; H, 4.79; N, 6.06. Found C, 75.26; H, 4.81; N, 6.01.

2.3.2

2.3.2 Biphenyl-4-carboxylic acid [5-(3-nitrobenzylidene)-4-oxo-2-phenylthiazolidin-3-yl]-amide (4b)

IR (KBr, cm⁻¹): 3253 (N–H), 3052 (C–H), 1657 (C⚌O), 1608–1485 (C⚌C), 1448–1435 (C–N), 1529–1581 (N–O). ¹H NMR (300 MHz, DMSO-d₆, δ ppm): 8.60–7.79 (m, 4H, Ar′ H), 8.05 (s, 1H, –NH), 7.78–7.47 (m 9H, Ar, H), 7.51–7.42 (m, 5H, Ar H), 7.40 (s, 1H, C⚌CH), 3.34 (s, 1H, –NCHS). Anal. Calcd. for C₂₉H₂₁N₃O₄S: C, 68.62; H, 4.17; N, 8.28. Found C, 68.66; H, 4.21; N, 8.22.

2.3.3

2.3.3 Biphenyl-4-carboxylic acid [5-(4-chlorobenzylidene)-4-oxo-2-phenylthiazolidin-3-yl]-amide (4c)

IR (KBr, cm⁻¹): 3403 (N–H), 2933 (C–H), 1716–1681 (C⚌O), 1606–1485 (C⚌C), 1436–1422 (C–N), 749–698 (C–Cl). ¹H NMR (300 MHz, DMSO-d₆, δ ppm): 8.49–7.77 (m, 9H, Ar H), 8.04 (s, 1H, –NH), 7.47–7.40 (m, 5H, Ar H), 7.67–7.50 (m, 4H, Ar H), 7.41 (s, 1H, C⚌CH), 3.92 (s, 1H, –NCHS). Anal. Calcd. for C₂₉H₂₁ClN₂O₂S: C, 70.08; H, 4.26; N, 5.64. Found C, 70.02; H, 4.30; N, 5.66.

2.3.4

2.3.4 Biphenyl-4-carboxylic acid [5-(3-bromobenzylidene)-4-oxo-2-phenylthiazolidin-3-yl]-amide (4d)

IR (KBr, cm⁻¹): 2993–2944 (C–H), 1717–1682 (C⚌O), 1605–1485 (C⚌C), 1436–1422 (C–N), 545 (C–Br). ¹H NMR (300 MHz, DMSO-d₆, δ ppm): 8.47–7.73 (m, 9H, Ar H), 8.07 (s, 1H, –NH), 7.46–7.42 (m, 5H, Ar H), 7.69–7.48 (m, 4H, Ar H), 7.38 (s, 1H, C⚌CH), 4.24 (s, 1H, –NCHS). Anal. Calcd. for C₂₉H₂₁BrN₂O₂S: C, 64.33; H, 3.91; N, 5.71. Found C, 64.29; H, 3.96; N, 5.70.

2.3.5

2.3.5 Biphenyl-4-carboxylic acid [5-(4-methoxybenzylidene)-4-oxo-2-phenylthiazolidin-3-yl]-amide (4e)

IR (KBr, cm⁻¹): 3269 (N–H), 3030–2927 (C–H), 1650 (C⚌O), 1607–1485 (C⚌C), 1447–1419 (C–N), 1253 (C–O–C). ¹H NMR (300 MHz, DMSO-d₆, δ ppm): 8.41–7.46 (m, 9H, Ar H), 8.03 (s, 1H, –NH), 7.40–7.22 (m, 4H, Ar′ H), 7.42 (s, 1H, C⚌CH), 7.38–7.26 (m, 5H, Ar′ H), 5.18 (s, 1H, –NCHS), 3.52 (s, 1H, –OCH). Anal. Calcd. for C₃₀H₂₄N₂O₃S: C, 73.13; H, 4.91; N, 5.69. Found C, 73.11; H, 4.95; N, 5.72.

2.3.6

2.3.6 Biphenyl-4-carboxylic acid [5-benzylidene-2-(3-bromophenyl)-4-oxothiazolidin-3-yl]-amide (4f)

IR (KBr, cm⁻¹): 3209 (N–H), 3030 (C–H), 1649 (C⚌O), 1606–1484 (C⚌C), 1447–1403 (C–N), 554–506 (C–Br). ¹H NMR (300 MHz, DMSO-d₆, δ ppm): 8.48–7.40 (m, 9H, Ar H), 8.04 (s, 1H, –NH), 7.68–7.38 (m, 5H, Ar′ H), 7.48–7.28 (m, 4H, Ar H), 7.46 (s, 1H, C⚌CH), 3.09 (s, 1H, –NCHS). Anal. Calcd. for C₂₉H₂₁BrN₂O₂S: C, 64.33; H, 3.91; N, 5.17. Found C, 64.31; H, 3.96; N, 5.14.

2.3.7

2.3.7 Biphenyl-4-carboxylic acid [2-(3-bromophenyl)-5-(3-nitrobenzylidene)-4-oxo-thiazolidin-3-yl]-amide (4g)

IR (KBr, cm⁻¹): 3261 (N–H), 3034 (C–H), 1655 (C⚌O), 1528 (N–O), 1608–1483 (C⚌C), 1445–1402 (C–N), 509 (C–Br). ¹H NMR (300 MHz, DMSO-d₆, δ ppm): 8.84–7.45 (m, 4H, Ar′ H), 8.06–7.37 (m, 9H, Ar H), 8.00 (s, 1H, –NH), 7.54–7.32 (m, 4H, Ar H), 7.50 (s, 1H, C⚌CH), 4.59 (s, 1H, –NCHS). Anal. Calcd. for C₂₉H₂₀BrN₃O₄S: C, 59.39; H, 3.44; N, 7.17. Found C, 59.43; H, 3.47; N, 7.21.

2.3.8

2.3.8 Biphenyl-4-carboxylic acid [2-(3-bromophenyl)-5-(4-chlorobenzylidene)-4-oxo-thiazolidin-3-yl]-amide (4h)

IR (KBr, cm⁻¹): 3282 (N–H), 3036 (C–H), 1651 (C⚌O), 1607–1447 (C⚌C), 1447 (C–N), 780–603 (C–Cl), 513 (C–Br). ¹H NMR (300 MHz, DMSO-d₆, δ ppm): 8.45–7.48 (m, 9H, Ar H), 8.00 (s, 1H, –NH), 7.58 (s, 1H, C⚌CH), 7.52–7.46 (m 4H, Ar′ H), 7.50–7.28 (m, 4H, Ar H), 3.02 (s, 1H, –NCHS). Anal. Calcd. for C₂₉H₂₀BrClN₂O₂S: C, 60.48; H, 3.50; N, 4.86. Found C, 60.43; H, 3.54; N, 4.83.

2.3.9

2.3.9 Biphenyl-4-carboxylic acid [5-(3-bromobenzylidene)-2-(3-bromophenyl)-4-oxo-thiazolidin-3-yl]-amide (4i)

IR (KBr, cm⁻¹): 3428 (N–H), 3044 (C–H), 1650 (C⚌O), 1607–1484 (C⚌C), 1447–1406 (C–N), 554–503 (C–Br). ¹H NMR (300 MHz, DMSO-d₆, δ ppm): 8.41–7.42 (m, 9H, Ar H), 8.03 (s, 1H, –NH), 7.62–7.30 (m, 4H, Ar′ H), 7.51 (s, 1H, C⚌CH), 7.46–7.26 (m, 4H, Ar′ H). Anal. Calcd. for C₂₉H₂₀Br₂N₂O₂S: C, 56.15; H, 3.25; N, 4.52. Found C, 56.20; H, 3.23; N, 4.57.

2.3.10

2.3.10 Biphenyl-4-carboxylic acid [2-(3-bromophenyl)-5-(4-methoxybenzylidene)-4-oxo-thiazolidin-3-yl]-amide (4j)

IR (KBr, cm⁻¹): 3428 (N–H), 3034 (C–H), 1650 (C⚌O), 1606–1473 (C⚌C), 1447–1403 (C–N), 1280–1253 (C–O–C), 553–531 (C–Br). ¹H NMR (300 MHz, DMSO-d₆, δ ppm): 8.05–7.44 (m, 9H, Ar H), 8.02 (s, 1H, –NH), 7.46–7.26 (m, 4H, Ar H), 7.41 (s, 1H, C⚌CH), 7.39–6.93 (m, 4H, Ar′ H), 4.60 (s, 1H, –NCHS), 3.48 (s, 1H, –OCH). Anal. Calcd. for C₃₀H₂₃BrN₂O₃S: C, 63.05; H, 4.06; N, 4.90. Found C, 63.01; H, 4.08; N, 4.86.

2.3.11

2.3.11 Biphenyl-4-carboxylic acid [5-benzylidene-2-(4-fluorophenyl)-4-oxothiazolidin-3-yl]-amide (4k)

IR (KBr, cm⁻¹): 3211 (N–H), 3038 (C–H), 1657 (C⚌O), 1606–1475 (C⚌C), 1445–1401 (C–N), 1233 (C–F). ¹H NMR (300 MHz, DMSO-d₆, δ ppm): 8.22–7.47 (m, 9H, Ar H), 8.03 (s, 1H, –NH), 7.56–7.37 (m, 5H, Ar′ H), 7.34–7.12 (m, 4H, Ar H), 7.52 (s, 1H, C⚌CH), 3.58 (s, 1H, –NCHS). Anal. Calcd. for C₂₉H₂₁FN₂O₂S: C, 72.48; H, 4.40; N, 5.83. Found C, 72.45; H, 4.37; N, 5.85.

2.3.12

2.3.12 Biphenyl-4-carboxylic acid [2-(4-fluorophenyl)-5-(3-nitrobenzylidene)-4-oxo-thiazolidin-3-yl]-amide (4l)

IR (KBr, cm⁻¹): 3245 (N–H), 3033 (C–H), 1651 (C⚌O), 1522 (N–O), 1605–1483 (C⚌C), 1445–1402 (C–N), 1226 (C–F). ¹H NMR (300 MHz, DMSO-d₆, δ ppm): 8.77–7.48 (m, 4H, Ar′ H), 8.11–7.35 (m, 9H, Ar H), 8.01 (s, 1H, –NH), 7.57–7.35 (4H, Ar H), 7.49 (s, 1H, C⚌CH), 4.31 (s, 1H, –NCHS). Anal. Calcd. for C₂₉H₂₀FN₃O₄S: C, 66.28; H, 3.84; N, 8.00. Found C, 66.25; H, 3.80; N, 6.03.

3 Antimicrobial evaluation

The synthesized compounds were evaluated for their in vitro antimicrobial activity against Gram positive bacteria: Staphylococcus aureus (MTCC 121), Bacillus subtilis (MTCC 96), Gram negative Escherichia coli (MTCC 40), Pseudomonas aeruginosa (MTCC 2453) and fungal strain: Candida albicans (MTCC 8184) and Aspergillus niger (MTCC 8189). Antimicrobial activity was assessed by serial two-fold dilution technique. Ciprofloxacin was used as a standard drug for antibacterial activity and clotrimazole was used as a standard drug for antifungal activity. All the compounds were dissolved in dimethyl sulfoxide to give a concentration of 10 μg ml⁻¹. Twofold dilutions of test and standard compounds were prepared in double strength nutrient broth I.P. (bacteria) or Sabouraud dextrose broth I.P. (Pharmacopoeia, 1996) (fungi). The stock solution was serially diluted to give concentrations of 25–0.78 μg ml⁻¹ in nutrient broth. The inoculum size was approximately 10⁶ colony forming units (CFU/ml). The tubes were incubated at 37 ± 1 °C for 24 h (bacteria) and 25 °C for 7 days (A. niger). After that, the inoculated culture tubes were macroscopically examined for turbidity. The culture tube showing turbidity (lower concentration) and the culture tube showing no turbidity (higher concentration) gave the minimum inhibitory concentration (MIC) for the compound. The MIC for antibacterial is given in Table 2 and MIC for antifungal is given in Table 3.

Table 2 In vitro antibacterial activity of the title compounds (4a–l).

Compound	Minimum inhibitory concentration (μg ml⁻¹)
Compound	E. coli (MTCC 40)	P. aeruginosa (MTCC 2453)	S. aureus (MTCC 121)	B. subtilis (MTCC 96)
4a	6.25	6.25	6.25	3.12
4b	6.25	3.12	3.12	1.56
4c	3.12	12.5	3.12	6.25
4d	12.5	6.25	3.12	6.25
4e	6.25	6.25	6.25	1.56
4f	6.25	3.12	3.12	3.12
4g	3.12	1.56	1.56	1.56
4h	12.5	6.25	6.25	6.25
4i	6.25	6.25	3.12	3.12
4j	1.56	12.5	3.12	1.56
4k	6.25	12.5	6.25	3.12
4l	12.5	3.12	6.25	6.25
Ciprofloxacin (standard drug)	0.01	0.25	0.15	0.12

Table 3 In vitro antifungal activity of the title compounds (4a–l).

Compound	Minimum inhibitory concentration (μg ml⁻¹)
Compound	C. albicans (MTCC 8184)	A. niger (MTCC 8189)
4a	3.12	6.25
4b	3.12	1.56
4c	1.56	3.12
4d	3.12	6.25
4e	3.12	1.56
4f	3.12	6.25
4g	1.56	3.12
4h	6.25	3.12
4i	1.56	1.56
4j	6.25	3.12
4k	6.25	12.5
4l	6.25	6.25
Clotrimazole (standard drug)	0.10	0.30

4 Results and discussion

In this study 12 novel compounds incorporating the scaffold of thiazolidinone have been synthesized and evaluated for antimicrobial activity. We described here a convenient approach to the preparation of biphenyl-4-carboxylic acid-5-(arylidene)-2-(aryl)-4-thiazolidinone. All compounds were synthesized according to Scheme 1. At the first stage, Schiff’s bases of biphenyl-4-carboxylic acid hydrazide and aromatic aldehydes were prepared. Further, reaction of these Schiff’s bases with thioglycollic acid in DMF and in presence of a small amount of ZnCl₂ yield the 2-substituted-4-thiazolidinone. 2-Substituted-4-thiazolidinone was reacted with aromatic aldehydes in the presence of sodium acetate and glacial acetic acid to yield the 2,5-disubstituted-4-thiazolidinone. Data obtained were found to be in good agreement with the calculated values of the proposed structure. All the synthesized compounds (4a–l) showed significant antimicrobial activity, against bacterial strain, E. coli (MIC 12.5–1.56 μg ml⁻¹), P. aeruginosa (MIC 12.5–1.56 μg ml⁻¹), S. aureus (MIC 6.25–1.56 μg ml⁻¹) and B. subtilis (MIC 6.25–1.56 μg ml⁻¹) as compared to the standard drug ciprofloxacin and against fungal strain, C. albicans (MIC 6.25–1.56 μg ml⁻¹) and A. niger (12.5–1.56 μg ml⁻¹) as compared to the standard drug clotrimazole. Compound 4g with its electron withdrawing group substitutions (bromo and nitro group) on aromatic rings was the most active compound against the bacterial strain. Compound 4i with their bromo substitution on both the aromatic rings was the most active compound against the fungal strain. More extensive study is also warranted to determine additional physicochemical and biological parameters to have a deeper insight into structure–activity relationship and to optimize the effectiveness of this series of molecules.

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Madhukar A., Kannappan N., Deep A., Kumar P., Kumar M., Verma P., . Int. J. Chem. Tech. Res.. 2009;1:1376.
Mujeebur R.V.P., Mukhtar S., Ansari W.H., . Eur. J. Med. Chem.. 2005;40:173.
Ottana R., Maccari R., Barreca M.L., Bruno G., Rotondo A., Rossi A., Paola R.D., Sautebin L., Cuzzocrea S., Vigorita M.G., . Bioorg. Med. Chem.. 2005;13:4243.
Pharmacopoeia, 1996. Pharmacopoeia of India, vol. II. Ministry of Health Department, Govt. of India, New Delhi, p. A-88.
Samir B., Wesam K., Ahmed A.F., . Eur. J. Med. Chem.. 2007;42:948.
Shah T.J., Desai V.A., . ARKIVOC. 2007;xiv:218.
Sharma R., Nagda D.P., Talesara G.L., . ARKIVOC. 2006;i:1.
Verma A., Saraf S.K., . Eur. J. Med. Chem.. 2008;43:897.
Vicini P., Geronikaki A., Anastasia K., Incerti M., Zani F., . Bioorg. Med. Chem.. 2006;14:3859.

Introduction

Experimental

Chemistry
General method
Spectral data

Antimicrobial evaluation

Results and discussion

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[1] Andres C.J., Bronson J.J., D’Andrea S.V., Deshpande M.S., Falk P.J., Young K.A.G., Harte W.E., Ho H.T., Stock D., Sun Y., Walsh A.W., . Bioorg. Med. Chem. Lett.. 2000;10:715.

[2] Balzarini J., Orzeszko B., Maurin J.K., Orzeszko A., . Eur. J. Med. Chem.. 2007;42:993.

[3] Bondock C., Khalifa W., Fadda A.A., . Eur. J. Med. Chem.. 2007;42:948.

[4] Deep A., Jain S., Sharma P.C., . Acta Pol. Pharm.. 2010;67:63.

[5] Deep A., Jain S., Sharma P.C., Verma P., Kumar M., Dora C.P., . Acta Pol. Pharm.. 2010;67:255.

[6] Goel B., Ram T., Tyagi R., Bansal E., Kumar A., Mukherjee D., Sinha J.M., . Eur. J. Med. Chem.. 1999;34:265.

[7] Gursoy A., Terzioglu N., . Turk. J. Chem.. 2005;29:247.

[8] Handan A., Oznur A., Seher B., Gulten O., Melten U., Dilek S., . Turk. J. Chem.. 2005;29:425.

[9] Knutsen L.J.S., Hobbs C.J., Earnshaw C.G., Fiumana A., Gilbert J., Mellor S.L., Radford F., Smith N.J., Birch P.J., Burley J.R., Ward S.D.C., James I.F., . Bioorg. Med. Chem. Lett.. 2007;17:662.

[10] Kumar, M., Jain, S., Deep, A., 2010. Lat. Am. J. Pharm., in press.

[11] Madhukar A., Kannappan N., Deep A., Kumar P., Kumar M., Verma P., . Int. J. Chem. Tech. Res.. 2009;1:1376.

[12] Mujeebur R.V.P., Mukhtar S., Ansari W.H., . Eur. J. Med. Chem.. 2005;40:173.

[13] Ottana R., Maccari R., Barreca M.L., Bruno G., Rotondo A., Rossi A., Paola R.D., Sautebin L., Cuzzocrea S., Vigorita M.G., . Bioorg. Med. Chem.. 2005;13:4243.

[14] Pharmacopoeia, 1996. Pharmacopoeia of India, vol. II. Ministry of Health Department, Govt. of India, New Delhi, p. A-88.

[15] Samir B., Wesam K., Ahmed A.F., . Eur. J. Med. Chem.. 2007;42:948.

[16] Shah T.J., Desai V.A., . ARKIVOC. 2007;xiv:218.

[17] Sharma R., Nagda D.P., Talesara G.L., . ARKIVOC. 2006;i:1.

[18] Verma A., Saraf S.K., . Eur. J. Med. Chem.. 2008;43:897.

[19] Vicini P., Geronikaki A., Anastasia K., Incerti M., Zani F., . Bioorg. Med. Chem.. 2006;14:3859.

Synthesis, characterization and antimicrobial evaluation of 2,5-disubstituted-4-thiazolidinone derivatives

Abstract

Keywords

Hydrazones

4-Thiazolidinone

Antibacterial and antifungal activity

1 Introduction

2 Experimental

2.1 Chemistry

2.2 General method

2.2.1 Synthesis of hydrazone (2)

2.2.2 Synthesis of 2-substituted-4-thiazolidinone (3a–c)

2.2.3 Synthesis of 2,5-disubstituted-4-thiazolidinone (4a–l)

2.3 Spectral data

2.3.1 Biphenyl-4-carboxylic acid (5-benzylidene-4-oxo-2-phenylthiazolidin-3yl)-amide (4a)

2.3.2 Biphenyl-4-carboxylic acid [5-(3-nitrobenzylidene)-4-oxo-2-phenylthiazolidin-3-yl]-amide (4b)

2.3.3 Biphenyl-4-carboxylic acid [5-(4-chlorobenzylidene)-4-oxo-2-phenylthiazolidin-3-yl]-amide (4c)

2.3.4 Biphenyl-4-carboxylic acid [5-(3-bromobenzylidene)-4-oxo-2-phenylthiazolidin-3-yl]-amide (4d)

2.3.5 Biphenyl-4-carboxylic acid [5-(4-methoxybenzylidene)-4-oxo-2-phenylthiazolidin-3-yl]-amide (4e)

2.3.6 Biphenyl-4-carboxylic acid [5-benzylidene-2-(3-bromophenyl)-4-oxothiazolidin-3-yl]-amide (4f)

2.3.7 Biphenyl-4-carboxylic acid [2-(3-bromophenyl)-5-(3-nitrobenzylidene)-4-oxo-thiazolidin-3-yl]-amide (4g)

2.3.8 Biphenyl-4-carboxylic acid [2-(3-bromophenyl)-5-(4-chlorobenzylidene)-4-oxo-thiazolidin-3-yl]-amide (4h)

2.3.9 Biphenyl-4-carboxylic acid [5-(3-bromobenzylidene)-2-(3-bromophenyl)-4-oxo-thiazolidin-3-yl]-amide (4i)

2.3.10 Biphenyl-4-carboxylic acid [2-(3-bromophenyl)-5-(4-methoxybenzylidene)-4-oxo-thiazolidin-3-yl]-amide (4j)

2.3.11 Biphenyl-4-carboxylic acid [5-benzylidene-2-(4-fluorophenyl)-4-oxothiazolidin-3-yl]-amide (4k)

2.3.12 Biphenyl-4-carboxylic acid [2-(4-fluorophenyl)-5-(3-nitrobenzylidene)-4-oxo-thiazolidin-3-yl]-amide (4l)

3 Antimicrobial evaluation

4 Results and discussion

References

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