Antimicrobial and antioxidant evaluation of new quinolone based aurone analogs

Hardik H. Jardosh; Manish P. Patel

doi:10.1016/j.arabjc.2014.05.014

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Original article

10 (

2_suppl

); S3781-S3791

doi:

10.1016/j.arabjc.2014.05.014

Antimicrobial and antioxidant evaluation of new quinolone based aurone analogs

Hardik H. Jardosh, Manish P. Patel^⁎

Department of Chemistry, Sardar Patel University, Vallabh Vidyanagar 388120, Gujarat, India

⁎Corresponding author. Tel.: +91 02692 226856. patelmanish1069@yahoo.com (Manish P. Patel)

Received: 2012-11-24, Accepted: 2014-5-27, Published: 2014-05-01

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

Peer review under responsibility of King Saud University.

Abstract

Abstract

A new series of aurones 3a–x has been synthesized by aldol condensation of N-(Un)substituted quinolone-3-carbaldehydes 1a–h and (Un)substituted benzofuran-3(2H)-ones 2a–c in the presence of 10 mol% NaOH in ethanol using a microwave irradiation method. All the aurone derivatives were screened for in vitro antimicrobial activity against a representative panel of bacterial and fungal pathogens using a broth microdilution method. The majority of the synthesized compounds elicited more or equipotent inhibitory action against all the tested bacterial and fungal strains. In vitro antioxidant activity was evaluated by the Ferric Reducing Antioxidant Power (FRAP) method. Compounds 3k and 3u displayed the highest antioxidant potential.

Keywords

Quinolones

Aurones

Antimicrobial activity

Antioxidant activity

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1 Introduction

Aurones are less studied subclass of flavonoids and found rarely in nature. Some naturally occurring aurones are maritimetin, sulfuretin and aureusidin which possess various hydroxylation patterns (Romussi and Pagani, 1970; Junior et al., 2008; Mohan and Joshi, 1989 ) (Fig. 1). Except those found in nature, aurones are a fertile source of medicinally important molecules possessing a wide spectrum of biological activities like antioxidant (Detsi et al., 2009), insect antifeedant (Morimoto et al., 2007), anticancer (Huang et al., 2007), antibacterial and anti-inflammatory (Bandgar et al., 2010). Moreover, the biological activities of aurones strongly depend on the number of hydroxyl groups present on Ring C (Dong et al., 2009; Lee et al., 2010).

On the other hand, quinolone is a core pharmacophore in the development of different biologically potent derivatives which found to possess various activities such as, anti-HIV (Gupta and Madan, 2012), antitumor (Li et al., 2006), anti-anaerobe (Schaumann and Rodloff, 2007), antibacterial (Sharma et al., 2015), anti-inflammatory and analgesic (Filippelli, 2010). Further, it has been established that the presence of an allyl group of heterocyclic nitrogen improves antimicrobial effectiveness and plays an important role in the development of new antimicrobial drugs (Praveen et al., 2011). Therefore, we selected the allyl group as a substituent at the nitrogen of the quinolone moiety.

The conventional method for the synthesis of aurones especially by using hydroxy/dihydroxy benzofuran-3(2H)-one encountered some problems such as, masking of OH groups, lengthy reaction time and poor yield due to side reaction (Detsi et al., 2009; Shin et al., 2011). Consequently, to overcome these drawbacks, the microwave-assisted organic synthesis (MAOS) approach was adopted for the synthesis of title compounds which improved selectivity of the reaction, shortened reaction time and made avoidable to prevent OH groups and gave a better yield.

Over the past few years, the development toward the construction of the efficient aurone scaffolds with appropriate biological activity by modifying or replacing the benzene ring with N-(Un)substituted indoles and different spacers have been made (Wallez et al., 2002; Gerby et al., 2007; Bursavicha et al., 2010; Haudecoeur et al., 2011 ) (Fig. 1). In the radiance of the above mentioned facts and as a prolongation of our investigation on the synthesis of biologically active heterocyclic compounds (Mungra et al., 2011; Thumar and Patel, 2011; Jardosh and Patel, 2011, 2012a,b; Sangani et al., 2012; Makawana et al., 2012; Shah et al., 2012 ), we were provoked to design and synthesize new quinolone based aurone analogs by using molecular hybridization approach and evaluate them as antimicrobials and antioxidants.

2 Experimental

2.1

2.1 General

Required acetic acid, hydrochloric acid, potassium carbonate, sodium acetate, N,N-dimethyl formamide, chloroform and methanol were procured from Merck, Darmstadt, Germany. Sodium hydroxide, zinc chloride, diethyl ether, resorcinol and phloroglucinol were obtained from S. D. Fine Chem Ltd., Vadodara, Gujarat, India. Allyl bromide, benzofuran-3(2H)-one and chloroacetonitrile were purchased from Sigma–Aldrich. Organic solvents were purified by standard methods (Furniss et al., 2004) and stored over molecular sieves and were used with further purification. The microwave assisted reactions are conducted in a “RAGA’s Modified Electromagnetic Microwave System” whereby microwaves are generated by magnetron at a frequency of 2450 MHz having adjustable output power levels i.e., 10 levels from 140 to 700 Watts and with an individual sensor for temperature control (fiber optic is used as an individual sensor for temperature control) with the attachment of the reflux condenser with constant stirring (thus avoiding the risk of high pressure development). Melting points of all the title compounds were determined by the open tube capillary method (using silicon oil 350 cst) and are uncorrected. All reactions were monitored by thin-layer chromatography (TLC, on aluminum plates coated with silica gel 60F₂₅₄, 0.25 mm thickness, Merck) carried out on fluorescent coated plates and detection of the components was made by exposure to iodine vapors or UV light. Elemental analysis (% C, H, N) was carried out by a Perkin–Elmer 2400 series-II elemental analyzer (Perkin–Elmer, USA) and all compounds are within ±0.4% of theory specified. The IR spectra were recorded on a Perkin–Elmer Spectrum GX FT-IR Spectrophotometer (Perkin–Elmer, USA) using potassium bromide pellets in the range of 4000–400 cm⁻¹ and frequencies of only characteristic peaks are expressed in cm⁻¹. ¹H NMR and ¹³C NMR spectra were recorded in DMSO-d₆ on a Bruker Avance 400F (MHz) spectrometer (Bruker Scientific Corporation Ltd., Switzerland) using TMS as an internal standard at 400 MHz and 100 MHz respectively. Chemical shifts are reported in parts per million (ppm). Mass spectra were scanned on a Shimadzu LCMS 2010 spectrometer. For antioxidant activity, UV spectra were recorded on a Shimadzu Type 160-A spectrometer.

2.2

2.2 General procedure for the synthesis of compounds 1a–h

Compounds 2-oxo-1,2-dihydroquinoline-3-carbaldehydes 1a–d and 1-allyl-2-oxo-1,2-dihydroquinoline-3-carbaldehydes 1e–h were prepared according to the literature method (Srivastava and Singh, 2005).

2.3

2.3 General procedure for the synthesis of compounds 2a–c

Compound benzofuran-3(2H)-one 2a was purchased from sigma aldrich. Compounds 6-hydroxybenzofuran-3(2H)-one 2b and 4,6-dihydroxybenzofuran-3(2H)-one 2c were prepared according to the literature method (Shriner and Grosser, 1942; Horning and Reisner, 1948).

2.4

2.4 General procedure for the synthesis of compounds 3a–x

In a 50 mL round-bottom flask, N-(Un)substituted quinolone-3-carbaldehydes 1a–h (3 mmol), (Un)substituted benzofuran-3(2H)-ones 2a–c (3 mmol), 10 mol% NaOH and 10 mL ethanol were taken and thoroughly mixed and irradiated in a microwave oven at 280 W (40% of output power) for 240 s. After the completion of the reaction (checked by TLC; eluent, chloroform:methanol::9:1), the solution was cooled to room temperature, the solid separated was filtered, washed well with R-spirit (10 ml), dried and recrystallized from chloroform–methanol (1:1) to get pure solid sample 3a–x. Physical, analytical and spectroscopic characterization data of the compounds 3a–x are given hereafter.

2.4.1

2.4.1 (Z)-3-((3-Oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3a)

Yield: 78%; m.p.: 226–228 °C; IR (KBr, ν, cm⁻¹): 3067 (ArC-H str.), 1693, 1602 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 6.87 (s, 1H, olefinic H), 7.24 (t, J₁ = 8.0 Hz, J₂ = 8.0 Hz, 1H, H₅), 7.30 (t, J₁ = 7.2 Hz, J₂ = 7.6 Hz, 1H, H_6′), 7.35 (d, J = 8.4 Hz, 1H, H₇), 7.46 (d, J = 8.4 Hz, 1H, H_7′), 7.59 (d, J = 8.4 Hz, 1H, H_8′), 7.67 (t, J₁ = 8.0 Hz, J₂ = 8.0 Hz, 1H, H₆), 7.83 (d, J = 8.4 Hz, 1H, H₄), 7.92 (d, J = 7.2 Hz, 1H, H_5′), 8.79 (s, 1H, H_4′), 12.02 (s, 1H, NH); ¹³C NMR (DMSO-d₆) δ_C (ppm): 109.26, 113.92, 117.10, 120.55, 120.96, 123.85, 125.82, 126.61, 129.24, 130.60, 132.20, 134.78, 137.03, 138.20, 152.05, 165.25 (16C, Ar-C + olefinic C⚌C), 168.42 (C⚌O), 181.57 (C⚌O); MS (m/z): 290.4 [M+1]⁺; Anal. Calcd for C₁₈H₁₁NO₃ (289.28 g/mol): C, 74.73; H, 3.83; N, 4.84; Found: C, 74.87; H, 4.08; N, 4.51.

2.4.2

2.4.2 (Z)-6-Methyl-3-((3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3b)

Yield: 75%; m.p.: 234–236 °C; IR (KBr, ν, cm⁻¹): 3067 (ArC-H str.), 1693, 1597 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 2.38 (s, 3H, CH₃), 6.85 (s, 1H, olefinic H), 7.23 (t, J₁ = 8.0 Hz, J₂ = 8.0 Hz, 1H, H₅), 7.36 (d, J = 8.4 Hz, 1H, H₇), 7.47 (d, J = 8.4 Hz, 1H, H_7′), 7.61 (d, J = 8.4 Hz, 1H, H_8′), 7.69 (t, J₁ = 8.0 Hz, J₂ = 8.0 Hz, 1H, H₆), 7.76 (d, J = 8.4 Hz, 1H, H₄), 7.85 (s, 1H, H_5′), 8.60 (s, 1H, H_4′), 12.01 (s, 1H, NH); ¹³C NMR (DMSO-d₆) δ_C (ppm): 21.69 (CH₃), 108.71, 114.06, 117.16, 120.57, 121.01, 123.84, 125.80, 126.63, 129.24, 130.63, 132.21, 134.71, 137.04, 138.25, 152.07, 165.28 (16C, Ar-C + olefinic C⚌C), 168.38 (C⚌O), 181.51 (C⚌O); MS (m/z): 304.2 [M+1]⁺; Anal. Calcd for C₁₉H₁₃NO₃ (303.31 g/mol): C, 75.24; H, 4.32; N, 4.62; Found: C, 74.98; H, 4.66; N, 4.88.

2.4.3

2.4.3 (Z)-6-Methoxy-3-((3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3c)

Yield: 71%; m.p.: 241–243 °C; IR (KBr, ν, cm⁻¹): 3082 (ArC-H str.), 1690, 1616 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 3.70 (s, 3H, OCH₃), 6.87 (s, 1H, olefinic H), 7.21 (t, J₁ = 8.0 Hz, J₂ = 8.0 Hz, 1H, H₅), 7.32 (d, J = 8.4 Hz, 1H, H₇), 7.43 (d, J = 8.4 Hz, 1H, H_7′), 7.58 (d, J = 8.4 Hz, 1H, H_8′), 7.65 (t, J₁ = 8.0 Hz, J₂ = 8.0 Hz, 1H, H₆), 7.73 (d, J = 8.4 Hz, 1H, H₄), 7.83 (s, 1H, H_5′), 8.62 (s, 1H, H_4′), 12.03 (s, 1H, NH); ¹³C NMR (DMSO-d₆) δ_C (ppm): 55.41 (OCH₃), 108.66, 113.97, 117.12, 120.51, 120.98, 123.81, 125.87, 126.57, 129.26, 130.62, 132.21, 134.73, 137.08, 138.24, 152.11, 165.28 (16C, Ar-C + olefinic C⚌C), 168.37 (C⚌O), 181.42 (C⚌O); MS (m/z): 320.3 [M+1]⁺; Anal. Calcd for C₁₉H₁₃NO₄ (319.31 g/mol): C, 71.47; H, 4.10; N, 4.39; Found: C, 71.32; H, 4.49; N, 4.47.

2.4.4

2.4.4 (Z)-6-Chloro-3-((3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3d)

Yield: 76%; m.p.: 261–263 °C; IR (KBr, ν, cm⁻¹): 3063 (ArC-H str.), 1697, 1601 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 6.84 (s, 1H, olefinic H), 7.24 (t, J₁ = 8.0 Hz, J₂ = 8.0 Hz, 1H, H₅), 7.35 (d, J = 8.4 Hz, 1H, H₇), 7.46 (d, J = 8.4 Hz, 1H, H_7′), 7.61 (d, J = 8.4 Hz, 1H, H_8′), 7.68 (t, J₁ = 8.0 Hz, J₂ = 8.0 Hz, 1H, H₆), 7.76 (d, J = 8.4 Hz, 1H, H₄), 7.85 (s, 1H, H_5′), 8.63 (s, 1H, H_4′), 12.05 (s, 1H, NH); ¹³C NMR (DMSO-d₆) δ_C (ppm): 109.52, 114.01, 117.35, 120.62, 121.08, 123.98, 125.91, 126.82, 129.36, 130.71, 132.41, 134.85, 137.12, 138.27, 152.18, 165.37 (16C, Ar-C + olefinic C⚌C), 168.51 (C⚌O), 182.15 (C⚌O); MS (m/z): 324.9 [M+1]⁺; Anal. Calcd for C₁₈H₁₀ClNO₃ (323.73 g/mol): C, 66.78; H, 3.11; N, 4.33; Found: C, 66.61; H, 3.02; N, 4.39.

2.4.5

2.4.5 (Z)-3-((6-Hydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3e)

Yield: 74%; m.p.: 234–236 °C; IR (KBr, ν, cm⁻¹): 3472 (O-H str.), 3067 (ArC-H str.), 1697, 1601 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 6.73 (dd, J₁ = 8.4 Hz, J₂ = 1.6 Hz, 1H, H₅), 6.87 (s, 1H, olefinic H), 7.09 (s, 1H, H₇), 7.31 (t, J₁ = 7.2 Hz, J₂ = 7.6 Hz, 1H, H_6′) 7.48 (d, J = 8.4 Hz, 1H, H_7′), 7.57 (d, J = 8.4 Hz, 1H, H_8′), 7.62 (d, J = 8.8 Hz, 1H, H₄), 7.91 (d, J = 7.2 Hz, 1H, H_5′), 8.78 (s, 1H, H_4′), 11.28 (s, 1H, OH), 12.02 (s, 1H, NH); ¹³C NMR (DMSO-d₆) δ_C (ppm): 99.43, 104.04, 113.11, 114.12, 115.71, 120.60, 123.16, 123.68, 126.59, 132.34, 132.81, 139.19, 141.01, 149.46, 167.26, 168.45 (16C, Ar-C + olefinic C⚌C), 160.42 (C⚌O), 181.51 (C⚌O); MS (m/z): 306.4 [M+1]⁺; Anal. Calcd for C₁₈H₁₁NO₄ (305.28 g/mol): C, 70.82; H, 3.63; N, 4.59; Found: C, 70.63; H, 3.95; N, 4.30.

2.4.6

2.4.6 (Z)-3-((6-Hydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)-6-methylquinolin-2(1H)-one (3f)

Yield: 71%; m.p.: 240–242 °C; IR (KBr, ν, cm⁻¹): 3410 (O-H str.), 3086 (ArC-H str.), 1693, 1593 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 2.37 (s, 3H, CH₃), 6.72 (dd, J₁ = 8.4 Hz, J₂ = 1.6 Hz, 1H, H₅), 6.84 (s, 1H, olefinic H), 7.04 (s, 1H, H₇), 7.22 (d, J = 8.4 Hz, 1H, H_7′), 7.37 (d, J = 8.4 Hz, 1H, H_8′), 7.62 (d, J = 8.4 Hz, 1H, H₄), 7.67 (s, 1H, H_5′), 8.69 (s, 1H, H_4′), 11.29 (br s, 1H, OH), 12.01 (s, 1H, NH); ¹³C NMR (DMSO-d₆) δ_C (ppm): 20.80 (CH₃), 99.31, 103.58, 113.15, 113.71, 115.56, 119.78, 124.43, 126.55, 128.84, 131.88, 133.42, 137.15, 141.31, 149.20, 167.17, 168.35 (16C, Ar-C + olefinic C⚌C), 161.18 (C⚌O), 181.55 (C⚌O); MS (m/z): 320.2 [M+1]⁺; Anal. Calcd for C₁₉H₁₃NO₄ (319.31 g/mol): C, 71.47; H, 4.10; N, 4.39; Found: C, 71.70; H, 4.02; N, 4.00.

2.4.7

2.4.7 (Z)-3-((6-Hydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)-6-methoxyquinolin-2(1H)-one (3g)

Yield: 72%; m.p.: 251–253 °C; IR (KBr, ν, cm⁻¹): 3448 (O-H str.), 3063 (ArC-H str.), 1690, 1597 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 3.75 (s, 3H, OCH₃), 6.70 (dd, J₁ = 8.4 Hz, J₂ = 1.6 Hz, 1H, H₅), 6.81 (s, 1H, olefinic H), 7.01 (s, 1H, H₇), 7.20 (d, J = 8.4 Hz, 1H, H_7′), 7.38 (d, J = 8.4 Hz, 1H, H_8′), 7.61 (d, J = 8.4 Hz, 1H, H₄), 7.69 (s, 1H, H_5′), 8.62 (s, 1H, H_4′), 11.18 (br s, 1H, OH), 11.98 (s, 1H, NH); ¹³C NMR (DMSO-d₆) δ_C (ppm): 55.62 (OCH₃), 99.36, 103.97, 113.17, 114.08, 115.65, 120.62, 123.10, 123.61, 126.55, 132.35, 132.83, 139.21, 141.12, 149.47, 167.28, 168.45 (16C, Ar-C + olefinic C⚌C), 160.41 (C⚌O), 181.56 (C⚌O); MS (m/z): 336.2 [M+1]⁺; Anal. Calcd for C₁₉H₁₃NO₅ (335.31 g/mol): C, 68.06; H, 3.91; N, 4.18; Found: C, 67.97; H, 3.75; N, 4.47.

2.4.8

2.4.8 (Z)-6-Chloro-3-((6-hydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3h)

Yield: 79%; m.p.: 271–273 °C; IR (KBr, ν, cm⁻¹): 3441 (O-H str.), 3082 (ArC-H str.), 1697, 1597 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 6.73 (dd, J₁ = 8.4 Hz, J₂ = 1.6 Hz, 1H, H₅), 6.85 (s, 1H, olefinic H), 7.07 (s, 1H, H₇), 7.25 (d, J = 8.4 Hz, 1H, H_7′), 7.38 (d, J = 8.4 Hz, 1H, H_8′), 7.63 (d, J = 8.4 Hz, 1H, H₄), 7.68 (s, 1H, H_5′), 8.71 (s, 1H, H_4′), 11.30 (br s, 1H, OH), 12.03 (s, 1H, NH); ¹³C NMR (DMSO-d₆) δ_C (ppm): 100.02, 104.23, 113.09, 114.24, 115.64, 120.74, 123.26, 123.72, 126.67, 132.45, 132.90, 139.16, 141.13, 149.62, 167.32, 168.52 (16C, Ar-C + olefinic C⚌C), 160.87 (C⚌O), 181.96 (C⚌O); MS (m/z): 340.6 [M+1]⁺; Anal. Calcd for C₁₈H₁₀ClNO₄ (339.73 g/mol): C, 63.64; H, 2.97; N, 4.12; Found: C, 63.41; H, 3.33; N, 4.39.

2.4.9

2.4.9 (Z)-3-((4,6-Dihydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3i)

Yield: 69%; m.p.: 245–247 °C; IR (KBr, ν, cm⁻¹): 3437 (O-H str.), 3086 (ArC-H str.), 1690, 1593 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 6.10 (s, 1H, H₅), 6.39 (s, 1H, olefinic H), 6.98 (s, 1H, H₇), 7.26 (t, J₁ = 7.2 Hz, J₂ = 7.6 Hz, 1H, H_6′) 7.37 (d, J = 8.4 Hz, 1H, H_7′), 7.48 (d, J = 8.4 Hz, 1H, H_8′), 7.75 (d, J = 7.2 Hz, 1H, H_5′), 8.58 (s, 1H, H_4′), 11.01 (br s, 2H, OH), 12.09 (s, 1H, NH) ppm; ¹³C NMR (DMSO-d₆) δ_C (ppm): 92.71, 96.44, 109.23, 120.33, 123.71, 133.24, 134.07, 137.18, 139.01, 139.32, 149.54, 149.81, 157.17, 159.01, 167.91, 168.04 (16C, Ar-C + olefinic C⚌C), 160.38 (C⚌O), 171.41 (C⚌O); MS (m/z): 322.1 [M+1]⁺; Anal. Calcd for C₁₈H₁₁NO₅ (321.28 g/mol): C, 67.29; H, 3.45; N, 4.36; Found: C, 67.60; H, 3.84; N, 4.07.

2.4.10

2.4.10 (Z)-3-((4,6-Dihydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)-6-methylquinolin-2(1H)-one (3j)

Yield: 61%; m.p.: 248–250 °C; IR (KBr, ν, cm⁻¹): 3410 (O-H str.), 3082 (ArC-H str.), 1682, 1628 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 2.37 (s, 3H, CH₃), 6.08 (s, 1H, H₅), 6.34 (s, 1H, olefinic H), 6.96 (s, 1H, H₇), 7.36 (d, J = 8.4 Hz, 1H, H_7′), 7.45 (d, J = 8.4 Hz, 1H, H_8′), 7.73 (s, 1H, H_5′), 8.57 (s, 1H, H_4′), 11.02 (br s, 2H, OH), 12.06 (s, 1H, NH); ¹³C NMR (DMSO-d₆) δ_C (ppm): 21.69 (CH₃), 92.73, 96.45, 109.22, 120.36, 123.73, 133.21, 134.02, 137.11, 139.03, 139.31, 149.58, 149.84, 157.12, 159.04, 167.95, 168.09 (16C, Ar-C + olefinic C⚌C), 160.41 (C⚌O), 171.32 (C⚌O); MS (m/z): 336.1 [M+1]⁺; Anal. Calcd for C₁₉H₁₃NO₅ (335.31 g/mol): C, 68.06; H, 3.91; N, 4.18; Found: C, 68.22; H, 4.29; N, 4.05.

2.4.11

2.4.11 (Z)-3-((4,6-Dihydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)-6-methoxyquinolin-2(1H)-one (3k)

Yield: 67%; m.p.: 262–264 °C; IR (KBr, ν, cm⁻¹): 3437 (O-H str.), 3067 (ArC-H str.), 1693, 1624 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 3.78 (s, 3H, OCH₃), 6.06 (s, 1H, H₅), 6.31 (s, 1H, olefinic H), 6.95 (s, 1H, H₇), 7.34 (d, J = 8.4 Hz, 1H, H_7′), 7.44 (d, J = 8.4 Hz, 1H, H_8′), 7.71 (s, 1H, H_5′), 8.54 (s, 1H, H_4′), 11.01 (br s, 2H, OH), 12.04 (s, 1H, NH); ¹³C NMR (DMSO-d₆) δ_C (ppm): 56.12 (OCH₃), 92.67, 96.41, 109.19, 120.27, 123.68, 133.21, 134.11, 137.14, 139.06, 139.36, 149.57, 149.83, 157.15, 159.04, 167.87, 168.05 (16C, Ar-C + olefinic C⚌C), 160.32 (C⚌O), 171.48 (C⚌O); MS (m/z): 352.1 [M+1]⁺; Anal. Calcd for C₁₉H₁₃NO₆ (351.31 g/mol): C, 64.96; H, 3.73; N, 3.99; Found: C, 65.28; H, 3.50; N, 3.72.

2.4.12

2.4.12 (Z)-6-Chloro-3-((4,6-dihydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3l)

Yield: 68%; m.p.: 271–273 °C; IR (KBr, ν, cm⁻¹): 3440 (O-H str.), 3064 (ArC-H str.), 1690, 1602 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 6.11 (s, 1H, H₅), 6.40 (s, 1H, olefinic H), 6.99 (s, 1H, H₇), 7.41 (d, J = 8.4 Hz, 1H, H_7′), 7.52 (d, J = 8.4 Hz, 1H, H_8′), 7.81 (s, 1H, H_5′), 8.62 (s, 1H, H_4′), 11.07 (br s, 2H, OH), 12.08 (s, 1H, NH); ¹³C NMR (DMSO-d₆) δ_C (ppm): 92.81, 96.46, 109.31, 120.27, 123.66, 133.34, 134.15, 137.23, 139.12, 139.41, 149.58, 149.86, 157.23, 159.06, 167.89, 168.05 (16C, Ar-C + olefinic C⚌C), 160.56 (C⚌O), 171.82 (C⚌O); MS (m/z): 356.9 [M+1]⁺; Anal. Calcd for C₁₈H₁₀ClNO₅ (355.73 g/mol): C, 60.77; H, 2.83; N, 3.94; Found: C, 60.54; H, 2.44; N, 4.18.

2.4.13

2.4.13 (Z)-1-Allyl-3-((3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3m)

Yield: 79%; m.p.: 232–234 °C; IR (KBr, ν, cm⁻¹): 3068 (ArC-H str.), 1692, 1603 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 4.96 (d, J = 4.0 Hz, 2H, N—CH₂—), 5.01 (d, J = 17.2 Hz, 1H, N—CH₂—CH⚌CH_trans), 5.14 (d, J = 10.4 Hz, 1H, N—CH₂—CCH⚌CH_cis), 5.91 (m, 1H, CH⚌CH₂), 6.86 (s, 1H, olefinic H), 7.22 (t, J₁ = 8.0 Hz, J₂ = 8.0 Hz, 1H, H₅), 7.28 (t, J₁ = 7.2 Hz, J₂ = 7.6 Hz, 1H, H_6′), 7.34 (d, J = 8.4 Hz, 1H, H₇), 7.46 (d, J = 8.4 Hz, 1H, H_7′), 7.58 (d, J = 8.4 Hz, 1H, H_8′), 7.68 (t, J₁ = 8.0 Hz, J₂ = 8.0 Hz, 1H, H₆), 7.84 (d, J = 8.4 Hz, 1H, H₄), 7.91 (d, J = 7.2 Hz, 1H, H_5′), 8.75 (s, 1H, H_4′); ¹³C NMR (DMSO-d₆) δ_C (ppm): 44.94 (allylic N—CH₂—CCH), 109.24, 113.84, 115.51, 117.12, 120.61, 121.14, 123.78, 125.65, 126.67, 129.34, 129.87, 131.02, 132.26, 134.72, 137.11, 138.24, 152.13, 165.36 (18C, Ar-C + olefinic and allylic C⚌C), 168.35 (C⚌O), 181.63 (C⚌O); MS (m/z): 330.2 [M+1]⁺; Anal. Calcd for C₂₁H₁₅NO₃ (329.35 g/mol): C, 76.58; H, 4.59; N, 4.25; Found: C, 76.47; H, 4.22; N, 4.08.

2.4.14

2.4.14 (Z)-1-Allyl-6-methyl-3-((3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3n)

Yield: 75%; m.p.: 245–247 °C; IR (KBr, ν, cm⁻¹): 3067 (ArC-H str.), 1697, 1597 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 2.32 (s, 3H, CH₃), 4.97 (d, J = 4.0 Hz, 2H, N—CH₂—), 5.02 (d, J = 17.2 Hz, 1H, N—CH₂—CH⚌CH_trans), 5.15 (d, J = 10.4 Hz, 1H, N—CH₂—CH⚌CH_cis), 5.93 (m, 1H, CH⚌CH₂), 6.85 (s, 1H, olefinic H), 7.24 (t, J₁ = 8.0 Hz, J₂ = 8.0 Hz, 1H, H₅), 7.37 (d, J = 8.4 Hz, 1H, H₇), 7.47 (d, J = 8.4 Hz, 1H, H_7′), 7.62 (d, J = 8.4 Hz, 1H, H_8′), 7.68 (t, J₁ = 8.0 Hz, J₂ = 8.0 Hz, 1H, H₆), 7.77 (d, J = 8.4 Hz, 1H, H₄), 7.85 (s, 1H, H_5′), 8.60 (s, 1H, H_4′); ¹³C NMR (DMSO-d₆) δ_C (ppm): 21.73 (CH₃), 44.95 (allylic N—CH₂—CH), 109.27, 113.81, 115.48, 117.16, 120.58, 121.20, 123.81, 125.72, 126.63, 129.41, 129.83, 131.07, 132.31, 134.66, 137.16, 138.31, 152.21, 165.33 (18C, Ar-C + olefinic and allylic C⚌C), 167.95 (C⚌O), 181.45 (C⚌O); MS (m/z): 344.3 [M+1]⁺; Anal. Calcd for C₂₂H₁₇NO₃ (343.38 g/mol): C, 76.95; H, 4.99; N, 4.08; Found: C, 76.61; H, 4.80; N, 4.32.

2.4.15

2.4.15 (Z)-1-Allyl-6-methoxy-3-((3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3o)

Yield: 71%; m.p.: 259–261 °C; IR (KBr, ν, cm⁻¹): 3063 (ArC-H str.), 1692, 1616 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 3.80 (s, 3H, OCH₃), 4.95 (d, J = 4.0 Hz, 2H, N—CH₂—), 5.01 (d, J = 17.2 Hz, 1H, N—CH₂—CH⚌CH_trans), 5.12 (d, J = 10.4 Hz, 1H, N—CH₂—CH⚌CH_cis), 5.90 (m, 1H, CH⚌CH₂), 6.87 (s, 1H, olefinic H), 7.22 (t, J₁ = 8.0 Hz, J₂ = 8.0 Hz, 1H, H₅), 7.34 (d, J = 8.4 Hz, 1H, H₇), 7.45 (d, J = 8.4 Hz, 1H, H_7′), 7.60 (d, J = 8.4 Hz, 1H, H_8′), 7.67 (t, J₁ = 8.0 Hz, J₂ = 8.0 Hz, 1H, H₆), 7.74 (d, J = 8.4 Hz, 1H, H₄), 7.83 (s, 1H, H_5′), 8.62 (s, 1H, H_4′); ¹³C NMR (DMSO-d₆) δ_C (ppm): 55.70 (OCH₃), 44.91 (allylic N—CH₂—CH), 109.31, 113.82, 115.43, 117.12, 120.47, 121.28, 123.84, 125.75, 126.60, 129.46, 129.84, 131.11, 132.29, 134.68, 137.21, 138.27, 152.25, 165.37 (18C, Ar-C + olefinic and allylic C⚌C), 167.83 (C⚌O), 181.51 (C⚌O); MS (m/z): 360.5 [M+1]⁺; Anal. Calcd for C₂₂H₁₇NO₄ (359.37 g/mol): C, 73.53; H, 4.77; N, 3.90; Found: C, 73.79; H, 4.82; N, 3.55.

2.4.16

2.4.16 (Z)-1-Allyl-6-chloro-3-((3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3p)

Yield: 76%; m.p.: 279–281 °C; IR (KBr, ν, cm⁻¹): 3082 (ArC-H str.), 1682, 1602 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 4.98 (d, J = 4.0 Hz, 2H, N—CH₂—), 5.05 (d, J = 17.2 Hz, 1H, N—CH₂—CH⚌CH_trans), 5.16 (d, J = 10.4 Hz, 1H, N—CH₂—CH⚌CH_cis), 5.95 (m, 1H, CH⚌CH₂), 6.88 (s, 1H, olefinic H), 7.27 (t, J₁ = 8.0 Hz, J₂ = 8.0 Hz, 1H, H₅), 7.38 (d, J = 8.4 Hz, 1H, H₇), 7.45 (d, J = 8.4 Hz, 1H, H_7′), 7.60 (d, J = 8.4 Hz, 1H, H_8′), 7.68 (t, J₁ = 8.0 Hz, J₂ = 8.0 Hz, 1H, H₆), 7.78 (d, J = 8.4 Hz, 1H, H₄), 7.87 (s, 1H, H_5′), 8.64 (s, 1H, H_4′); ¹³C NMR (DMSO-d₆) δ_C (ppm): 44.97 (allylic N—CH₂—CH), 109.38, 113.85, 115.51, 117.27, 120.55, 121.34, 123.91, 125.88, 126.71, 129.53, 129.89, 131.07, 132.25, 134.70, 137.32, 138.19, 152.36, 165.44 (18C, Ar-C + olefinic and allylic C⚌C), 168.21 (C⚌O), 181.69 (C⚌O); MS (m/z): 364.9 [M+1]⁺; Anal. Calcd for C₂₁H₁₄ClNO₃ (363.79 g/mol): C, 69.33; H, 3.88; N, 3.85; Found: C, 69.40; H, 4.00; N, 3.61.

2.4.17

2.4.17 (Z)-1-Allyl-3-((6-hydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3q)

Yield: 76%; m.p.: 231–233 °C; IR (KBr, ν, cm⁻¹): 3472 (O-H str.), 3067 (ArC-H str.), 1697, 1601 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 4.96 (d, J = 4.0 Hz, 2H, N—CH₂—), 5.00 (d, J = 17.2 Hz, 1H, N—CH₂—CH⚌CH_trans), 5.15 (d, J = 10.4 Hz, 1H, N—CH₂—CH⚌CH_cis), 5.93 (m, 1H, CH⚌CH₂), 6.72 (dd, J₁ = 8.4 Hz, J₂ = 1.6 Hz, 1H, H₅), 6.86 (s, 1H, olefinic H), 7.08 (s, 1H, H₇), 7.30 (t, J₁ = 7.2 Hz, J₂ = 7.6 Hz, 1H, H_6′) 7.46 (d, J = 8.4 Hz, 1H, H_7′), 7.59 (d, J = 8.4 Hz, 1H, H_8′), 7.63 (d, J = 8.8 Hz, 1H, H₄), 7.92 (d, J = 7.2 Hz, 1H, H_5′), 8.79 (s, 1H, H_4′), 11.28 (s, 1H, OH); ¹³C NMR (DMSO-d₆) δ_C (ppm): 44.98 (allylic N—CH₂—CH), 99.40, 103.84, 113.16, 114.04, 115.68, 117.07, 120.57, 123.11, 123.62, 126.61, 130.60, 132.37, 132.78, 139.13, 141.08, 149.41, 167.22, 168.42 (18C, Ar-C + olefinic and allylic C⚌C), 160.48 (C⚌O), 181.58 (C⚌O); MS (m/z): 345.9 [M+1]⁺; Anal. Calcd for C₂₁H₁₅NO₄ (345.35 g/mol): C, 73.03; H, 4.38; N, 4.06; Found: C, 72.75; H, 4.30; N, 3.70.

2.4.18

2.4.18 (Z)-1-Allyl-3-((6-hydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)-6-methylquinolin-2(1H)-one (3r)

Yield: 78%; m.p.: 245–247 °C; IR (KBr, ν, cm⁻¹): 3448 (O-H str.), 3067 (ArC-H str.), 1693, 1597 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 2.38 (s, 3H, CH₃), 4.98 (d, J = 4.0 Hz, 2H, N—CH₂—), 5.02 (d, J = 17.2 Hz, 1H, N—CH₂—CH⚌CH_trans), 5.17 (d, J = 10.4 Hz, 1H, N—CH₂—CH⚌CH_cis), 5.94 (m, 1H, CH⚌CH₂), 6.70 (dd, J₁ = 8.4 Hz, J₂ = 1.6 Hz, 1H, H₅), 6.82 (s, 1H, olefinic H), 7.01 (s, 1H, H₇), 7.21 (d, J = 8.4 Hz, 1H, H_7′), 7.42 (d, J = 8.4 Hz, 1H, H_8′), 7.57 (d, J = 8.4 Hz, 1H, H₄), 8.04 (s, 1H, H_5′), 8.88 (s, 1H, H_4′), 11.32 (br s, 1H, OH); ¹³C NMR (DMSO-d₆) δ_C (ppm): 21.82 (CH₃), 44.92 (allylic N—CH₂—CH), 99.44, 103.81, 113.17, 114.08, 115.64, 117.09, 120.51, 123.16, 123.65, 126.63, 130.54, 132.33, 132.75, 139.14, 141.04, 149.43, 167.26, 168.45 (18C, Ar-C + olefinic and allylic C⚌C), 160.43 (C⚌O), 181.52 (C⚌O); MS (m/z): 360.2 [M+1]⁺; Anal. Calcd for C₂₂H₁₇NO₄ (359.37 g/mol): C, 73.53; H, 4.77; N, 3.90; Found: C, 73.66; H, 4.70; N, 3.65.

2.4.19

2.4.19 (Z)-1-Allyl-3-((6-hydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)-6-methoxyquinolin-2(1H)-one (3s)

Yield: 71%; m.p.: 256–258 °C; IR (KBr, ν, cm⁻¹): 3437 (O-H str.), 3086 (ArC-H str.), 1693, 1616 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 3.77 (s, 3H, OCH₃), 4.97 (d, J = 4.0 Hz, 2H, N—CH₂—), 5.01 (d, J = 17.2 Hz, 1H, N—CH₂—CH⚌CH_trans), 5.16 (d, J = 10.4 Hz, 1H, N—CH₂—CH⚌CH_cis), 5.92 (m, 1H, CH⚌CH₂), 6.68 (dd, J₁ = 8.4 Hz, J₂ = 1.6 Hz, 1H, H₅), 6.79 (s, 1H, olefinic H), 6.99 (s, 1H, H₇), 7.18 (d, J = 8.4 Hz, 1H, H_7′), 7.40 (d, J = 8.4 Hz, 1H, H_8′), 7.55 (d, J = 8.4 Hz, 1H, H₄), 8.01 (s, 1H, H_5′), 8.82 (s, 1H, H_4′), 11.29 (br s, 1H, OH); ¹³C NMR (DMSO-d₆) δ_C (ppm): 55.81 (OCH₃), 44.87 (allylic N—CH₂—CH), 99.41, 103.86, 113.14, 114.12, 115.71, 117.10, 120.56, 123.17, 123.64, 126.61, 130.55, 132.30, 132.72, 139.15, 141.06, 149.42, 167.29, 168.41 (18C, Ar-C + olefinic and allylic C⚌C), 160.48 (C⚌O), 181.58 (C⚌O); MS (m/z): 376.3 [M+1]⁺; Anal. Calcd for C₂₂H₁₇NO₅ (375.37 g/mol): C, 70.39; H, 4.56; N, 3.73; Found: C, 70.04; H, 4.72; N, 3.64.

2.4.20

2.4.20 (Z)-1-Allyl-6-chloro-3-((6-hydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3t)

Yield: 73%; m.p.: 259–261 °C; IR (KBr, ν, cm⁻¹): 3448 (O-H str.), 3067 (ArC-H str.), 1697, 1593 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 4.91 (d, J = 4.0 Hz, 2H, N—CH₂—), 4.98 (d, J = 17.2 Hz, 1H, N—CH₂—CH⚌CH_trans), 5.01 (d, J = 10.4 Hz, 1H, N—CH₂—CH⚌CH_cis), 5.94 (m, 1H, CH⚌CH₂), 6.71 (dd, J₁ = 8.4 Hz, J₂ = 1.6 Hz, 1H, H₅), 6.81 (s, 1H, olefinic H), 6.99 (s, 1H, H₇), 7.22 (d, J = 8.4 Hz, 1H, H_7′), 7.41 (d, J = 8.4 Hz, 1H, H_8′), 7.59 (d, J = 8.4 Hz, 1H, H₄), 8.02 (s, 1H, H_5′), 8.90 (s, 1H, H_4′), 11.39 (br s, 1H, OH); ¹³C NMR (DMSO-d₆) δ_C (ppm): 45.15 (allylic N—CH₂—CH), 99.70, 104.51, 112.86, 114.21, 117.16, 118.15, 121.81, 124.83, 126.14, 127.12, 129.10, 131.49, 132.50, 137.69, 139.70, 149.73, 167.44, 168.41 (18C, Ar-C + olefinic and allylic C⚌C), 160.16 (C⚌O), 181.41 (C⚌O); MS (m/z): 380.6 [M+1]⁺; Anal. Calcd for C₂₁H₁₄ClNO₄ (379.79 g/mol): C, 66.41; H, 3.72; N, 3.69; Found: C, 66.13; H, 3.73; N, 3.91.

2.4.21

2.4.21 (Z)-1-Allyl-3-((4,6-dihydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3u)

Yield: 65%; m.p.: 241–243 °C; IR (KBr, ν, cm⁻¹): 3441 (O-H str.), 3082 (ArC-H str.), 1697, 1593 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 4.97 (d, J = 4.0 Hz, 2H, N—CH₂—), 5.03 (d, J = 17.2 Hz, 1H, N—CH₂—CH⚌CH_trans), 5.16 (d, J = 10.4 Hz, 1H, N—CH₂—CH⚌CH_cis), 5.97 (m, 1H, CH⚌CH₂), 6.08 (s, 1H, H₅), 6.33 (s, 1H, olefinic H), 6.95 (s, 1H, H₇), 7.24 (t, J₁ = 7.2 Hz, J₂ = 7.6 Hz, 1H, H_6′) 7.38 (d, J = 8.4 Hz, 1H, H_7′), 7.46 (d, J = 8.4 Hz, 1H, H_8′), 7.72 (d, J = 7.2 Hz, 1H, H_5′), 8.68 (s, 1H, H_4′), 11.09 (br s, 2H, OH); ¹³C NMR (DMSO-d₆) δ_C (ppm): 45.00 (allylic N—CH₂—CH), 99.40, 113.09, 114.14, 115.66, 116.94, 120.57, 123.09, 123.59, 125.92, 130.55, 132.26, 132.69, 139.11, 141.15, 149.39, 167.21, 168.40, 169.44 (18C, Ar-C + olefinic and allylic C⚌C), 160.49 (C⚌O), 181.56 (C⚌O); MS (m/z): 362.3 [M+1]⁺; Anal. Calcd for C₂₁H₁₅NO₅ (361.35 g/mol): C, 69.80; H, 4.18; N, 3.88; Found: C, 69.91; H, 4.35; N, 3.61.

2.4.22

2.4.22 (Z)-1-Allyl-3-((4,6-dihydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)-6-methylquinolin-2(1H)-one (3v)

Yield: 62%; m.p.: 257–259 °C; IR (KBr, ν, cm⁻¹): 3410 (O-H str.), 3082 (ArC-H str.), 1682, 1628 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 2.38 (s, 3H, CH₃), 4.94 (d, J = 4.0 Hz, 2H, N—CH₂—), 5.00 (d, J = 16.8 Hz, 1H, N—CH₂—CH⚌CH_trans), 5.16 (d, J = 9.2 Hz, 1H, N—CH₂—CH⚌CH_cis), 5.94 (m, 1H, CH⚌CH₂), 6.06 (s, 1H, H₅), 6.30 (s, 1H, olefinic H), 6.94 (s, 1H, H₇), 7.36 (d, J = 8.4 Hz, 1H, H_7′), 7.43 (d, J = 8.4 Hz, 1H, H_8′), 7.69 (s, 1H, H_5′), 8.64 (s, 1H, H_4′), 11.02 (br s, 2H, OH); ¹³C NMR (DMSO-d₆) δ_C (ppm): 21.78 (CH₃), 44.58 (allylic N—CH₂—CH), 92.82, 96.67, 109.26, 113.90, 120.55, 123.85, 132.20, 133.39, 133.87, 137.03, 139.11, 139.82, 149.62, 149.77, 157.08, 159.03, 168.05, 168.17 (18C, Ar-C + olefinic and allylic C⚌C), 160.38 (C⚌O), 171.49 (C⚌O); MS (m/z): 375.9 [M+1]⁺; Anal. Calcd for C₂₂H₁₇NO₅ (375.37 g/mol): C, 70.39; H, 4.56; N, 3.73; Found: C, 70.00; H, 4.35; N, 3.76.

2.4.23

2.4.23 (Z)-1-Allyl-3-((4,6-dihydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)-6-methoxyquinolin-2(1H)-one (3w)

Yield: 64%; m.p.: 262–264 °C; IR (KBr, ν, cm⁻¹): 3441 (O-H str.), 3067 (ArC-H str.), 1690, 1624 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 3.80 (s, 3H, OCH₃), 4.92 (d, J = 4.0 Hz, 2H, N—CH₂—), 5.01 (d, J = 16.8 Hz, 1H, N—CH₂—CH⚌CH_trans), 5.14 (d, J = 9.2 Hz, 1H, N—CH₂—CH⚌CH_cis), 5.95 (m, 1H, CH⚌CH₂), 6.05 (s, 1H, H₅), 6.28 (s, 1H, olefinic H), 6.91 (s, 1H, H₇), 7.34 (d, J = 8.4 Hz, 1H, H_7′), 7.41 (d, J = 8.4 Hz, 1H, H_8′), 7.68 (s, 1H, H_5′), 8.62 (s, 1H, H_4′), 11.01 (br s, 2H, OH); ¹³C NMR (DMSO-d₆) δ_C (ppm): 44.49 (allylic N—CH₂—CH), 55.62 (OCH₃), 93.01, 97.13, 109.28, 113.95, 120.56, 123.87, 132.24, 133.41, 133.84, 137.04, 139.16, 139.79, 149.61, 149.73, 157.11, 159.08, 168.12, 168.23 (18C, Ar-C + olefinic and allylic C⚌C), 160.42 (C⚌O), 172.52 (C⚌O); MS (m/z): 392.5 [M+1]⁺; Anal. Calcd for C₂₂H₁₇NO₆ (391.37 g/mol): C, 67.51; H, 4.38; N, 3.58; Found: C, 67.78; H, 4.44; N, 3.94.

2.4.24

2.4.24 (Z)-1-Allyl-6-chloro-3-((4,6-dihydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3x)

Yield: 68%; m.p.: 274–276 °C; IR (KBr, ν, cm⁻¹): 3472 (O-H str.), 3063 (ArC-H str.), 1692, 1602 (C⚌O str.); ¹H NMR (DMSO-d₆) δ_H (ppm): 4.99 (d, J = 4.0 Hz, 2H, N—CH₂—), 5.08 (d, J = 16.8 Hz, 1H, N—CH₂—CH⚌CH_trans), 5.18 (d, J = 9.2 Hz, 1H, N—CH₂—CH⚌CH_cis), 5.96 (m, 1H, CH⚌CH₂), 6.09 (s, 1H, H₅), 6.34 (s, 1H, olefinic H), 6.98 (s, 1H, H₇), 7.37 (d, J = 8.4 Hz, 1H, H_7′), 7.45 (d, J = 8.4 Hz, 1H, H_8′), 7.70 (s, 1H, H_5′), 8.65 (s, 1H, H_4′), 11.12 (br s, 2H, OH); ¹³C NMR (DMSO-d₆) δ_C (ppm): 44.81 (allylic N—CH₂—CH), 93.52, 97.36, 109.42, 113.98, 120.68, 123.96, 132.44, 133.57, 133.91, 137.21, 139.35, 139.90, 149.56, 149.88, 157.06, 159.13, 168.18, 168.30 (18C, Ar-C + olefinic and allylic C⚌C), 161.22 (C⚌O), 172.85 (C⚌O); MS (m/z): 396.8 [M+1]⁺; Anal. Calcd for C₂₁H₁₄ClNO₅ (395.79 g/mol): C, 63.73; H, 3.57; N, 3.54; Found: C, 63.74; H, 3.26; N, 3.50.

3 Results and discussion

3.1

3.1 Chemistry

The synthetic precursors 2-oxo-1,2-dihydroquinoline-3-carbaldehydes 1a–d were synthesized by refluxing respective 2-chloro-3-formyl quinolines in the presence of 70% acetic acid and 1-allyl-2-oxo-1,2-dihydroquinoline-3-carbaldehydes 1e–h were prepared by electrophile favored N-alkylation of 1a–d in the presence of K₂CO₃ in DMF at room temperature (Srivastava and Singh, 2005) (Scheme 1). Precursors 2b and 2c were prepared by reaction of resorcinol/phloroglucinol with chloroacetonitrile respectively, via a Hoesch acylation to give an iminium salt and then hydrolyzed under acidic condition (Shriner and Grosser, 1942; Horning and Reisner, 1948) (Scheme 1).

Synthetic pathway for the synthesis of intermediates 1a–h and 2b,c.

The aurones 3a–x were synthesized by condensation of (Un)substituted benzofuran-3(2H)-one 2a–c with various N-(Un)substituted quinolone-3-carbaldehyde 1a–h by microwave irradiation in the presence of 10 mol% NaOH in ethanol at 280 W for 240 s (Scheme 2). This procedure significantly shortened the reaction time and made it unnecessary to protect the phenolic hydroxyl groups prior to aldol condensation. Products were obtained in moderate to good yield (61–79%).

Representative route for the synthesis of compounds 3a–x.

The reaction was optimized by varying the mole ratio of NaOH (Table 1). A mixture of 1a–h and 2a–c was subjected to microwave irradiation (280 W) by varying mole ratio of NaOH 2.5, 5.0, 7.5, 10.0 and 12.5 mol%. It was observed that when the amount of NaOH was increased to 10.0 mol%, the reaction rate was increased within a shorter reaction time (240 s). On the other hand, further increase in the amount of NaOH resulted into the sticky mass which required ice-water work up and gave poor yield. The formation of products was continuously checked by thin layer chromatography (TLC) at regular time interval to optimize the reaction time and it was found that the reaction was completed within 240 s. The above results showed that the best results were obtained when the reaction was carried out with 10.0 mol% of NaOH under microwave irradiation at 280 W for 240 s.

Table 1 Optimization of catalyst mol% and reaction time for aldol condensation of 6-chloro-2-oxo-1,2-dihydroquinoline-3-carbaldehyde and 6-hydroxybenzofuran-3(2H)-one.^a

Entry	NaOH (mol%)	Time (s)	Yield^b (%)
1	2.5	540	21
2	5.0	420	34
3	7.5	360	53
4	10.0	240	79
5	12.5	240	61

a Reaction conditions: 6-chloro-2-oxo-1,2-dihydroquinoline-3-carbaldehyde (3.0 mmol) and 6-hydroxybenzofuran-3(2H)-one (3.0 mmol), ethanol, MWI, 280 W.

b Isolated yield.

In accordance with the mechanism suggested in the literature (Lee, 2009), the reaction of the substituted benzofuran-3(2H)-one 2a–c with N-(Un)substituted quinolone-3-carbaldehydes 1a–h proceeded via an aldol condensation. Under the basic conditions of the reaction, 2a–c forms an enolate which reacts with the electron deficient carbonyl carbon of the aldehyde with loss of water to give the desired aurone (Scheme 3).

Conceivable mechanistic pathway for the formation of aurones 3a–x.

The structures of the title compounds 3a–x were confirmed by FT-IR, ¹H NMR, ¹³C NMR, mass spectra and elemental analysis. The absorption bands for the title compounds in IR-spectra were observed in the range of 1593–1697 cm⁻¹ which corresponds to two –C⚌O group stretching frequencies. The aromatic C–H stretching bands were observed in the range of 3063–3086 cm⁻¹. The IR spectrum of compounds 3e–l and 3q–x that exhibited a characteristic absorption band in the range of 3410–3472 cm⁻¹ is mainly attributed to the presence of the OH group. In all cases, a single geometric isomer (Z) was obtained and confirmed by ¹H NMR. It was known from the literature that the assignment of configuration in aurones can be possible on the basis of chemical shifts of the olefinic proton (Huke and Gorlitzer, 1969). It has been well established that the Z-isomer is thermodynamically more stable than E-isomer and the chemical shift of the olefinic proton is deshielded in the E-isomer of aurones and appears downfield (⩾7.01 ppm) compared to the Z-isomer (⩾6.70 ppm) (Hastings and Heller, 1972; Thakkar and Cushman, 1995; Beney et al., 2001 ). The ¹H NMR data of the title compounds 3a–x showed that the olefinic proton appeared up field around δ 6.28 ppm to δ 6.88 ppm. These values indicate that all the synthesized compounds 3a–x were geometrically pure and were exclusively cis (Z)-isomers. In the ¹³C NMR spectral data of the compounds 3a–x the signals observed at around δ 160.16 to δ 168.51 are attributed to the carbonyl carbon of the quinolone ring and signals observed at around δ 171.49 to 182.15 are attributed to the carbonyl carbon of the benzofuranone ring. The obtained elemental analysis values are in good agreement with theoretical data. Mass spectra of all the title compounds gave expected [M+1]⁺ peak corresponding to proposed molecular mass.

3.2

3.2 Antimicrobial activity

Interestingly, most of the synthesized aurone analogs were observed to be promising leads and possessing excellent antibacterial and antifungal activities when compared with the standard drugs (Table 2). Reviewing the antimicrobial activity data of aurone derivatives 3a–x revealed that, against Gram positive bacteria Staphylococcus aureus, compound 3w (MIC = 12.5 μg/mL) was found to exhibit marvelous activity compared to ampicillin, chloramphenicol and ciprofloxacin while compound 3s (MIC = 50 μg/mL) was as effective as chloramphenicol and ciprofloxacin. Compounds 3k (MIC = 62.5 μg/mL), 3i (MIC = 100 μg/mL), 3g and 3o (MIC = 125 μg/mL) as well as 3u (MIC = 200 μg/mL) were found to be more potent while compounds 3a, 3c, 3f, 3l, 3n, 3q and 3t (MIC = 250 μg/mL) were found to be equipotent compared to ampicillin. Against Bacillus subtilis, compound 3g (MIC = 25 μg/mL) was found to possess fabulous activity when compared to all the standard drugs employed. Compound 3w (MIC = 62.5 μg/mL) exhibited significant activity while compounds 3k, 3s and 3v (MIC = 100 μg/mL) exhibited comparable activity to ampicillin and norfloxacin. Against Clostridium tetani, compound 3i (MIC = 50 μg/mL) was found to be equally potent with chloramphenicol and norfloxacin. Compounds 3o and 3s (MIC = 62.5 μg/mL) displayed more efficacy than ampicillin and ciprofloxacin. Compounds 3u and 3w (MIC = 100 μg/mL) were found to possess comparable activity with norfloxacin. Compounds 3a, 3k and 3v (MIC = 125 μg/mL) were found to be more potent while compounds 3c, 3d, 3g, 3j, 3l, 3p, 3r and 3t (MIC = 250 μg/mL) were found to be equipotent when compared with ampicillin.

Table 2 Antimicrobial activity results of compounds 3a–x.

	Compound				Minimum Inhibitory Concentration (MIC, μg/mL)
	Compound				Gram positive bacteria			Gram negative bacteria			Fungi
	R₁	R₂	R₃	R₄	S.A.	B.S.	C.T.	E.C.	P.A.	V.C.	C.A.	A.C.
3a	H	H	H	H	250	250	125	250	500	250	1000	500
3b	CH₃	H	H	H	500	200	500	100	125	100	500	>1000
3c	OCH₃	H	H	H	250	125	250	500	250	250	>1000	>1000
3d	Cl	H	H	H	500	250	250	250	500	125	100	100
3e	H	H	OH	H	500	125	500	200	250	200	500	1000
3f	CH₃	H	OH	H	250	250	500	50	100	250	1000	500
3g	OCH₃	H	OH	H	125	25	250	250	250	250	500	>1000
3h	Cl	H	OH	H	500	250	500	125	200	500	250	250
3i	H	H	OH	OH	100	125	50	125	200	62.5	>1000	500
3j	CH₃	H	OH	OH	500	250	250	125	62.5	50	>1000	1000
3k	OCH₃	H	OH	OH	62.5	100	125	250	125	200	1000	1000
3l	Cl	H	OH	OH	250	200	250	200	25	100	500	250
3m	H	Allyl	H	H	500	250	500	200	250	250	1000	125
3n	CH₃	Allyl	H	H	250	125	500	62.5	100	250	>1000	250
3o	OCH₃	Allyl	H	H	125	250	62.5	125	125	125	1000	500
3p	Cl	Allyl	H	H	500	500	250	500	125	100	125	100
3q	H	Allyl	OH	H	250	250	500	125	200	125	500	500
3r	CH₃	Allyl	OH	H	500	200	250	62.5	100	125	1000	>1000
3s	OCH₃	Allyl	OH	H	50	100	62.5	200	125	200	1000	>1000
3t	Cl	Allyl	OH	H	250	200	250	100	125	250	100	250
3u	H	Allyl	OH	OH	200	125	100	100	100	20	>1000	1000
3v	CH₃	Allyl	OH	OH	500	100	125	50	12.5	62.5	1000	>1000
3w	OCH₃	Allyl	OH	OH	12.5	62.5	100	100	125	125	500	500
3x	Cl	Allyl	OH	OH	500	250	500	200	125	125	250	100
Ampicillin					250	100	250	100	n.t.	100	n.t.	n.t.
Chloramphenicol					50	50	50	50	50	50	n.t.	n.t.
Ciprofloxacin					50	50	100	25	25	25	n.t.	n.t.
Norfloxacin					10	100	50	10	10	10	n.t.	n.t.
Nystatin					n.t.	n.t.	n.t.	n.t.	n.t.	n.t.	100	100
Griseofulvin					n.t.	n.t.	n.t.	n.t.	n.t.	n.t.	500	100

S.A.: Staphylococcus aureus (MTCC 96); B.S.: Bacillus subtilis (MTCC 441); C.T.: Clostridium tetani (MTCC 449); E.C.: Escherichia coli (MTCC 443); P.A.: Pseudomonas aeruginosa (MTCC 1688); V.C.: Vibrio cholerae (MTCC 3906); C.A.: Candida albicans (MTCC 227); A.C.: Aspergillus clavatus (MTCC 1323).

MTCC: Microbial Type Culture Collection.

n.t.: not tested.

Bold numbers indicate more or equally potent compounds compared to standard drugs.

Against Gram negative bacteria Escherichia coli, compounds 3f and 3v (MIC = 50 μg/mL) showed equal potency to chloramphenicol. Compounds 3n and 3r (MIC = 62.5 μg/mL) exhibited excellent activity while compounds 3b, 3t, 3u and 3w (MIC = 100 μg/mL) were found to be equally potent when compared with ampicillin. Against Pseudomonas aeruginosa, compound 3v (MIC = 12.5 μg/mL) was found to possess marvelous activity while compound 3l (MIC = 25 μg/mL) was found to have similar activity when compared with ciprofloxacin. Against Vibrio cholerae, compound 3u (MIC = 20 μg/mL) showed admirable activity comparable to all the standard drugs employed except norfloxacin while compound 3j (MIC = 50 μg/mL) displayed equal activity with chloramphenicol. Compounds 3i and 3v (MIC = 62.5 μg/mL) showed more potency while compounds 3b, 3l and 3p (MIC = 100 μg/mL) showed equal potency when compared with ampicillin.

Against fungi Candida albicans, compounds 3d and 3t (MIC = 100 μg/mL) were found to be equipotent to nystatin. Compounds 3p (MIC = 125 μg/mL), 3h and 3x (MIC = 250 μg/mL) were found to be more potent while compounds 3b, 3e, 3g, 3l, 3q and 3w (MIC = 500 μg/mL) were found to be equipotent when compared with griseofulvin. Against Aspergillus clavatus, compounds 3d, 3p and 3x (MIC = 100 μg/mL) exhibited equal potency to nystatin and griseofulvin.

The investigation of the structure–activity relationship (SAR) revealed that compounds with an electron donating group on ring A (R₁ = OCH₃) gave better results against Gram positive bacteria e.g., 3g, 3k, 3o, 3s and 3w. Compounds having an electron donating (R₁ = CH₃) group showed excellent antibacterial potency against Gram negative bacteria e.g. 3f, 3j, 3h, 3r and 3w. Compounds with an electron withdrawing group (R₁ = Cl) were found to be less potent against any of the bacterial pathogens except compound 3l, but found to have significant activity against fungal species e.g. 3d, 3h, 3p, 3t and 3x. Compounds having unsubstituted ring A viz., (R₁ = H) were found to be active against S. aureus and C. tetani, e.g., 3a, 3i and 3u.

Furthermore, compounds having a lipophilic group (R₂ = allyl) in ring B exhibited more potency against a representative panel of employed species compared to N-unsubstituted quinolone (R₂ = H), e.g., 3n, 3o, 3p, 3r, 3s, 3t, 3u, 3v and 3w. Compounds containing two OH groups (R₃ = R₄ = OH) on ring C showed remarkable inhibition of the growth of employed pathogens compared to one OH group (R₃ = OH) and unsubstituted ring C (R₃ = R₄ = H), e.g., 3i, 3k, 3u, 3v and 3w. From the SAR study of the title derivatives, it is interesting to note that a minor alteration in the peripheral substitutions present on ring A, B and C may have a pronounced effect on the antimicrobial activity.

3.3

3.3 Antioxidant activity

All the aurone derivatives were evaluated for their antioxidant activity using the FRAP method (Table 3). Among the compounds tested in this study, compounds 3k and 3u (R₃ = R₄ = OH) displayed a relatively high antioxidant power while compound 3f (R₃ = OH, R₄ = H) and compounds 3i, 3j, 3l, 3v, 3w and 3x (R₃ = R₄ = OH) exhibited a better ferric reducing power. The antioxidant activity of title derivatives revealed that compounds having two OH groups can easily give electron for the reduction of Fe⁺³-TPTZ to Fe⁺²-TPTZ complex. It is worth to mention that antioxidant activity strongly depends on the number of hydroxyl group present on ring C.

Table 3 Antioxidant activity results of compounds 3a–x.

Compd	ΔOD (593 nm)	FRAP value^a	Compd	ΔOD (593 nm)	FRAP value^a
3a	1.162	233.47	3n	0.946	190.07
3b	0.912	183.24	3o	1.098	220.61
3c	1.304	262.01	3p	0.996	200.12
3d	0.992	199.32	3q	1.505	302.39
3e	1.932	388.19	3r	1.610	323.49
3f	2.272	456.51	3s	1.896	380.96
3g	2.221	446.26	3t	1.428	286.92
3h	1.806	362.87	3u	2.138	495.69
3i	2.464	470.37	3v	2.283	458.72
3j	2.291	460.32	3w	2.440	490.26
3k	2.024	495.08	3x	2.312	464.54
3l	2.249	451.88	A.A.	2.476	–
3m	0.779	156.52

A.A. = ascorbic acid.

Concentration of compounds used = 200 μg/mL.

Concentration of standard (A.A.) = 176 μg/mL.

a A.A. mm/100 g sample.

4 Biological evaluation

4.1

4.1 Antimicrobial screening

The in vitro antimicrobial activity of all the compounds and standard drugs were assessed against three representatives of Gram positive bacteria viz. S. aureus (MTCC 96), B. subtilis (MTCC 441), and C. tetani (MTCC 449); three Gram negative bacteria E. coli (MTCC 443), P. aeruginosa (MTCC 1688), V. cholerae (MTCC 3906) and two fungi C. albicans (MTCC 227) and A. clavatus (MTCC 1323) by the broth microdilution MIC (Minimum Inhibitory Concentration) method according to the National Committee for Clinical Laboratory Standards (NCCLS, 2002). The strains employed for the activity were procured from (MTCC-Micro Type Culture Collection) the Institute of Microbial Technology, Chandigarh. Mueller Hinton Broth was used as nutrient medium to grow and dilute the compound suspension for the test bacteria and Sabouraud Dextrose Broth was used for fungal nutrition. Ampicillin, chloramphenicol, ciprofloxacin and norfloxacin were used as standard antibacterial drugs, whereas griseofulvin and nystatin were used as standard antifungal drugs.

Bacterial strains were primarily inoculated into Mueller–Hinton agar and, after overnight growth, a number of colonies were directly suspended in saline solution until the turbidity matched the turbidity of the McFarland standard (approximately 10⁸ CFU/mL) i.e., inoculum size for test strain was adjusted to 10⁸ CFU/mL (Colony Forming Unit per milliliter) well by comparing the turbidity (turbidimetric method). Similarly, fungi were inoculated on Sabouraud Dextrose Broth, the procedures of inoculum standardization were also similar. DMSO was used as diluents/vehicle to get the desired concentration of synthesized compounds and standard drugs to test upon standard microbial strains i.e. the compounds were dissolved in DMSO and the solutions were diluted with a culture medium. Each compound and standard drugs were diluted obtaining 2000 μg/mL concentration, as a stock solution. By further progressive dilutions with the test medium, the required concentrations were obtained for primary and secondary screening. In primary screening 1000, 500, and 250 μg/mL concentrations of the synthesized compounds were taken. The active compounds found in this primary screening were further diluted to obtain 200, 125, 100, 62.5 and 50 μg/mL concentrations for secondary screening to test in a second set of dilution against all microorganisms. Briefly, the control tube containing no antibiotic is immediately sub cultured [before inoculation] by spreading a loopful evenly over a quarter of plate of medium suitable for the growth of the test organism. The tubes are then put for incubation at 37 °C for 24 h for bacteria and 48 h for fungi. Growth or a lack of growth in the tubes containing the antimicrobial agent was determined by comparison with the growth control, indicated by turbidity. The lowest concentration that completely inhibited visible growth of the organism was recorded as the minimal inhibitory concentration (MIC, μg/mL) i.e., the amount of growth from the control tube before incubation (which represents the original inoculum) is compared. A set of tubes containing only seeded broth and the solvent controls were maintained under identical conditions so as to make sure that the solvent had no influence on strain growth. The test mixture should contain 10⁸ CFU/mL organisms. The interpretation of the results was based on griseofulvin and nystatin breakpoints for fungi and based on ampicillin, chloramphenicol, ciprofloxacin and norfloxacin for bacterial pathogens.

4.2

4.2 Ferric Reducing Antioxidant Power (FRAP) assay

Ferric Reducing Antioxidant Power (FRAP) of newly synthesized compounds was determined chemically using a modified FRAP method reported by Benzie and Strain (Benzie and Strain, 1996). The FRAP method depends upon the reduction of ferric tripyridyltriazine complex (Fe⁺³-TPTZ) to the ferrous tripyridyltriazine (Fe⁺²-TPTZ) by a reductant (antioxidant) at a low pH. This ferrous tripyridyltriazine complex has an intensive blue color and can be monitored at 593 nm. The antioxidant potentials of the compounds 3a–x were estimated as their power to reduce the TPTZ–Fe(III) complex to TPTZ–Fe(II) complex. The ascorbic acid was used as a standard antioxidant compound. The results were expressed as ascorbic equivalent (mmol/100 g compound) and are listed in (Table 2).

4.2.1

4.2.1 Reagents

Buffer solution: 0.187 g sodium acetate and 1.6 mL acetic acid dissolved in double distilled water to make 100 mL.

TPTZ: 0.155 g TPTZ was dissolved in 100 mL 40 mM HCl.

FeCl₃ solution: 0.324 g FeCl₃ was dissolved in 100 mL distilled water.

Standard ascorbic acid: 0.176 g standard ascorbic acid was dissolved in 100 mL distilled water.

Fe(II)–TPTZ(2,4,6-tripyridyl-s-triazine) reagent was prepared by mixing a 10.0 mL TPTZ solution, 10 mL FeCl₃ solution and 100 mL acetate buffer of pH 3.6. A mixture of 200.0 μL sample solution and 3 mL of Fe(II)TPTZ reagent was incubated at 37 °C for 15 min. The absorbance of color complex Fe(II)TPTZ was measured at 593 nm using ascorbic acid as standard. The results were expressed as ascorbic equivalent (mmol/100 g compound).

Ascorbic acid taken = 1.99 × 10⁻⁴ mm.

Sample taken = 0.04 mg.

The Ferric Reducing Antioxidant Power (FRAP) can be calculated using the following equation: $FRAP value (mm A.A. / 100 g sample) = \frac{Δ {OD}_{593 nm} of sample}{Δ {OD}_{593 nm} of standard} \times \frac{mm of standard}{sample weight (mg)} \times 10^{5}$

5 Conclusion

The protocol offers an expeditious synthesis of quinolone based aurones 3a–x by the use of NaOH-an ecofriendly base. An adaptation of MAOS approach prevents the side reaction to occur and facilitate the selectivity in the synthesis of title compound to afford products in good yield. Reviewing the antimicrobial and antioxidant activity data, it has been concluded that majority of the compounds were found to be active against the representative panel of bacterial and fungal pathogens and compounds 3k and 3u were found to be the most efficient antioxidants of the series. Also, SAR study indicates that antimicrobial activity of the title compounds depends on the nature of peripheral substituents present on ring A, B and C while antioxidant activity strongly depends on OH groups present on ring C. Hence, the molecular hybridization of benzofuranone with quinolone nuclei gives the resultant aurone scaffold with fascinating antioxidant and antimicrobial activity. It is worth to mention that aurone derivatives bearing quinolone nucleus can be a vital spot in the medicinal research.

Acknowledgements

The authors are thankful to the Department of Chemistry, Sardar Patel University for providing research facilities. We are also thankful to the Vaibhav Analytical Laboratory, Ahmedabad for the FT-IR and Sophisticated Instrumentation Centre for Applied Research and Training (SICART), Vallabh Vidyanagar for elemental analysis. As well as Oxygen Healthcare Research Pvt. Ltd, Ahmedabad for providing mass spectrometry facilities and Dhanji P. Rajani, Microcare Laboratory, Surat for antimicrobial screening of the compounds reported herein. One of the authors is grateful to UGC, New Delhi for a Research Fellowship in Sciences for Meritorious Students.

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Show Sections

[1] Bandgar B.P., Patil S.A., Korbad B.L., Biradar S.C., Nile S.N., Khobragade C.N., . Eur. J. Med. Chem.. 2010;45:3223-3227.

[2] Beney C., Mariotte A., Boumendjel A., . Heterocycles. 2001;55:967-972.

[3] Benzie I.F., Strain J.J., . Anal. Biochem.. 1996;239:70-76.

[4] Bursavicha M.G., Brooijmans N., Feldberg L., Hollander I., Kim S., Lombardi S., Park K., Mallon R., Gilbert A.M., . Bioorg. Med. Chem. Lett.. 2010;20:2586-2590.

[5] Detsi A., Majdalani M., Kontogiorgis C.A., Hadjipavlou-Litina D., Kefalas P., . Bioorg. Med. Chem.. 2009;17:8073-8085.

[6] Dong X., Liu T., Yan J., Wu P., Chen J., Hu Y., . Bioorg. Med. Chem.. 2009;17:716-726.

[7] Filippelli W., . Arch. Pharm. Pharm. Med. Chem.. 2010;343:561-569.

[8] Furniss B.S., Hannaford A.J., Smith P.W.G., Tatchell A.R., . Vogel’s textbook of practical organic chemistry (fifth ed.). Harlow: Longman scientific and technical; 2004.

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Antimicrobial and antioxidant evaluation of new quinolone based aurone analogs

Abstract

Abstract

Keywords

Quinolones

Aurones

Antimicrobial activity

Antioxidant activity

1 Introduction

2 Experimental

2.1 General

2.2 General procedure for the synthesis of compounds 1a–h

2.3 General procedure for the synthesis of compounds 2a–c

2.4 General procedure for the synthesis of compounds 3a–x

2.4.1 (Z)-3-((3-Oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3a)

2.4.2 (Z)-6-Methyl-3-((3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3b)

2.4.3 (Z)-6-Methoxy-3-((3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3c)

2.4.4 (Z)-6-Chloro-3-((3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3d)

2.4.5 (Z)-3-((6-Hydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3e)

2.4.6 (Z)-3-((6-Hydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)-6-methylquinolin-2(1H)-one (3f)

2.4.7 (Z)-3-((6-Hydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)-6-methoxyquinolin-2(1H)-one (3g)

2.4.8 (Z)-6-Chloro-3-((6-hydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3h)

2.4.9 (Z)-3-((4,6-Dihydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3i)

2.4.10 (Z)-3-((4,6-Dihydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)-6-methylquinolin-2(1H)-one (3j)

2.4.11 (Z)-3-((4,6-Dihydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)-6-methoxyquinolin-2(1H)-one (3k)

2.4.12 (Z)-6-Chloro-3-((4,6-dihydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3l)

2.4.13 (Z)-1-Allyl-3-((3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3m)

2.4.14 (Z)-1-Allyl-6-methyl-3-((3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3n)

2.4.15 (Z)-1-Allyl-6-methoxy-3-((3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3o)

2.4.16 (Z)-1-Allyl-6-chloro-3-((3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3p)

2.4.17 (Z)-1-Allyl-3-((6-hydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3q)

2.4.18 (Z)-1-Allyl-3-((6-hydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)-6-methylquinolin-2(1H)-one (3r)

2.4.19 (Z)-1-Allyl-3-((6-hydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)-6-methoxyquinolin-2(1H)-one (3s)

2.4.20 (Z)-1-Allyl-6-chloro-3-((6-hydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3t)

2.4.21 (Z)-1-Allyl-3-((4,6-dihydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3u)

2.4.22 (Z)-1-Allyl-3-((4,6-dihydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)-6-methylquinolin-2(1H)-one (3v)

2.4.23 (Z)-1-Allyl-3-((4,6-dihydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)-6-methoxyquinolin-2(1H)-one (3w)

2.4.24 (Z)-1-Allyl-6-chloro-3-((4,6-dihydroxy-3-oxobenzofuran-2(3H)-ylidene)methyl)quinolin-2(1H)-one (3x)

3 Results and discussion

3.1 Chemistry

3.2 Antimicrobial activity

3.3 Antioxidant activity

4 Biological evaluation

4.1 Antimicrobial screening

4.2 Ferric Reducing Antioxidant Power (FRAP) assay

4.2.1 Reagents

5 Conclusion

Acknowledgements

References

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