Abstract
A series of 3-(5-chloro-2-oxoindolin-3-ylideneamino)-2-arylthiazolidin-4-ones 4a–k and 5-chloro-3-(3-chloro-2-oxo-4-arylazetidin-1-ylimino)indolin-2-ones 5a–k was synthesized. The structures of final compounds were confirmed by analytical (C, H, N) and spectral (FT-IR, 1H NMR, 13C NMR and Mass) data. The synthesized compounds were screened for possible antibacterial and antifungal activity. Compounds 4c, 4f, 4g, 4h, 4i, 4j, 5c, 5f, 5g, 5h, 5i and 5j showed substantially significant activity.
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Introduction
Isatin derivatives have been found to possess potent wide spectrum of activities like antibacterial, antifungal (Bondock et al., 2008; Gupta and Narayana, 1997; Pandeya et al., 1999; Sridhar et al., 2001), antitubercular (Aboul-Fadl et al., 2003; Karali et al., 2007), anticonvulsant (Verma et al., 2004; Sridhar et al., 2002), anticancer (Vine et al., 2007) and antioxidant (Andreani et al., 2010). The 2-azetidinone (β-lactam) ring system is a common structural feature in number of broad spectrum β-lactam antibiotics like penicillins and cephalosporins which have been widely used as chemotherapeutic agents to treat bacterial infections and diseases. These molecules operate by forming a covalent adduct with membrane-bound bacterial transpeptidases, which are also known as penicillin binding proteins (PBPs), involved in the biosynthesis of cell wall. These therapeutic agents prevent the construction of cell wall and eventually lead to cell lysis and death. Moreover, due to their β-lactamase inhibitory action, 2-azetidinone-based heterocycles represent an attractive target of contemporary organic synthesis. A large numbers of 2-azetidinones (Arnould et al., 1992; Halve et al., 2007; Keri et al., 2009) were reported to possess antibacterial and antifungal activity. The 4-thiazoldinone nucleus has drawn many attentions due to its various activities like antimicrobial (Vicini et al., 2008), anti-HIV (Chen et al., 2009; Rao et al., 2004; Rawal et al., 2005) anticancer (Abdel-Aziz et al., 2010; Lv et al., 2010) and antihypertensive (Bhandari et al., 2009).
Various chemotherapeutic drugs are in use but due to increase in microbial resistance against these drugs, there is a need to develop new, potent and fast-acting antimicrobial drugs. In the light of these observations, it was planned to synthesize a series of isatin derivatives by incorporating the azetidinone/thiazolidinone moiety at third position of isatin nucleus with an aim to get better antibacterial as well as antifungal activity.
Results and discussion
Chemistry
The synthetic routes of compounds are outlined in Scheme 1. The compound 5-chloroindoline-2,3-dione 1 was prepared according to reported method (Marvel and Hiers, 1941). The condensation of 5-chloroindoline-2,3-dione 1 with hydrazine hydrate in ethanol afforded 5-chloro-3-hydrazonoindolin-2-one 2 (Khan et al., 2002, 2009). Compound 2 on further reaction with different substituted aromatic aldehydes in presence of 2–3 drops of glacial acetic acid in ethanol yielded the corresponding 5-chloro-3-[(arylidene)hydrazono]indoline-2-ones 3a–3k. Compounds 3a–3k, further undergoes cyclization with thioglycolic acid in presence of anhydrous ZnCl2 and with chloroacetylchloride in presence of triethylamine (Et3N) to afford 3-(5-chloro-2-oxoindolin-3-ylideneamino)-2-arylthiazolidin-4-ones 4a–4k (Agarwal et al., 2006) and 5-chloro-3-(3-chloro-2-oxo-4-arylazetidin-1-ylimino)indolin-2-ones 5a–5k (Bhati and Kumar, 2008), respectively.
3a–k, 4a–k and 5a–k. Ar = phenyl,2-chlorophenyl, 4-chlorophenyl,3-methoxyphenyl,2-hydorxyphenyl, 4-hydorxyphenyl,4-dimethylaminophenyl, 4-methoxyphenyl,4-fluorophenyl,4-nitorphenyl and 2-furan
The thiazolidi-4-ones and azetidi-2-ones are formed by cycloaddition mechanism (Soleiman, 2011). The formation of compounds 3a–k was evidenced by appearance of a band between 1675 and 1703 cm−1 (N=CH) in the IR spectrum and appearance of a singlet between δ 8.58–9.1 for one proton of –N=CH–Ar in the 1H NMR spectra also supports their structures. Cycloaddition of thioglycolic acid to 3a–3k resulted into compounds 4a–4k which was confirmed by the presence of a band between 1760 and 1771 cm−1 (C=O of β-thialactum ring) in the IR spectra and a singlet in between δ 3.1–3.5 of two protons of CH2 of thiazolidinone ring and 4.3–4.8 of –CH–Ar in the 1H NMR spectra. Cycloaddition of chloroacetylchloride to 3a–3k resulted into compounds 5a–5k which was confirmed by the presence of a band between 1745 and 1760 cm−1 (C=O of β-lactam ring) in the IR spectra and a singlet in between δ 4.25–4.9 of –CH–Cl and 5.2–5.5 of –CH–Ar in the 1H NMR spectra.
Antimicrobial activity
All the synthesized compounds were screened for their possible antibacterial and antifungal activities by determining minimum inhibitory concentrations (MICs) in μg ml−1 against selected strains. The MICs was determined by broth dilution method (Srinivas et al., 2006). The MIC was determined for each compound along with ciprofloxacin as standard control and the results are presented in Tables 1 and 2. The MIC values of 12 derivatives against tested organisms exhibited significant activity with a degree of variation. It was found that 4-thiazolidinone derivatives of 5-chloroisatin displayed substantially significant activity: compound 4c against S. hominis, B. pumilus, B. cereus, S. typhi, E. coli and P. aeroginosa; 4f against S. epiderimidis, S. hominis, B. pumilus, P. vulgaris, S. typhi, K. pneumonia and P. aeroginosa; 4g against S. aureus, S. hominis, B. pumilus, P. mirabilis and S. typhi; 4h against B. subtilis, S. epidermidis, P. mirabilis, S. typhi and K. pneumonia; 4i against S. epiderimidis, S. hominis, B. pumilus, B. cereus, S. typhi and P. aeroginosa; 4j against M. luteus, S. aureus, S. hominis, S. typhi and P. aeroginosa.
In case of 2-azetidinone derivatives of 5-chloroisatin, the substantially significant activity is exhibited by: compound 5c against B. subtilis, S. hominis, B. pumilus, P. vulgaris, S. typhi and K. pneumonia; 5f against B. subtilis, S. epiderimidis, B. pumilus, B. cereus, P. vulgaris, P. mirabilis, S. typhi, E. coli and P. aeroginosa; 5g against S. epiderimidis, B. pumilus, P. vulgaris, S. typhi, K. pneumonia, E. coli and P. aeroginosa; 5h against S. epiderimidis, M. luteus, B. pumilus, B. cereus, S. typhi, K. pneumonia, E. coli and P. aeroginosa; 5i against B. subtilis, S. hominis, P. mirabilis and S. typhi; 5j against B. subtilis, M. luteus, B. pumilus, B. cereus, P. vulgaris, P. mirabilis, S. typhi, K. pneumonia and P. aeroginosa.
The antifungal activity (MIC) of all the synthesized compounds was determined by using clotrimazole as standard control. From the series of 4-thiazolidinone, derivatives 4c, 4f, 4g, 4h, 4i and 4j exhibited substantially significant activity against A. niger, A. Awamori, C. albicans, A. alternate, M. canis, R. solani, T. longiformis, A. flavus, F. solani, T. viride, A. flavus and A. fumigatus. Also, the compounds 5c, 5f, 5g, 5h, 5i and 5j of 2-azetidinone series showed substantially significant activity against A. niger, A. Awamori, C. albicans, A. alternate, M. canis, R. solani, T. longiformis, A. flavus, F. solani, T. viride, A. flavus and A. fumigatus. The compounds 4a, 4d, 4k, 5a, 5d and 5k showed significant activity and 4b, 4e, 5b and 5e are found to be inactive against all screened strains of bacteria and fungi.
Conclusions
In this study, we report synthesis and characterization of a series of 3-(5-chloro-2-oxoindolin-3-ylideneamino)-2-arylthiazolidin-4-one and 5-chloro-3-(3-chloro-2-oxo-4-arylazetidin-1-ylimino)indolin-2-one from 5-chloro-3-[(arylidene)hydrazono]indoline-2-one although the synthesis of spirothiazolidinone (Bhambi et al., 2009; Dandia et al., 2006) and spiroazetidinone (Dandia et al., 2007; Singh and Luntha, 2009) derivatives of isatin are reported previously. The activity data reveals that the compounds 4c, 4f, 4g, 4h, 4i, 4j, 5c, 5f, 5g, 5h, 5i and 5j having electron withdrawing as well as electron releasing substitution at fourth position of the phenyl ring exhibits good antibacterial as well as antifungal activities. The compounds 4d and 5d having electron releasing substituents at third position of the phenyl ring exhibits moderate activity. In compounds 4b, 4e, 5b and 5e electron withdrawing substituents at second position of phenyl ring are found to be inactive. In conclusion, the substitution at the fourth position may enhance activity and substitution at second position may decrease the activity.
Experimental protocols
General
All reagents and solvents used in study are of analytical grade and have been procured locally. The progress of the reaction is monitored by TLC and the products are purified through recrystallization. The melting points (m. p.) were determined in one-end-open capillary method and are uncorrected. The CATA-2R microwave was used for microwave assisted reaction. IR spectra were recorded on Shimadzu FT-IR 8400-S spectrophotometer using potassium bromide (KBr) pellet. The 1H NMR spectra were acquired on Varian AMX 300 NMR instrument using CDCl3 or DMSO-d 6 as the solvent and TMS as the internal reference (chemical shifts in δ, ppm); 13C NMR was performed on Varian AMX 300 (100 MHz) spectrometer using solutions in CDCl3 or DMSO-d 6 and mass spectra were acquired on API 2000 spectrometer. The elemental analysis (C, H, N) of compounds was performed on Elementar Vario EL III elemental analyzer.
General procedure for the synthesis of 5-chloro-3-[(arylidene)hydrazono] indoline-2-one (3a–k)
5-Chloro-3-hydrazonoindolin-2-one (2, 0.1 mol), various substituted aromatic aldehydes (0.1 mol) and two drops of glacial acetic acid in 50 ml absolute alcohol was refluxed for 2 h. The reaction mixture was cooled at room temperature. The solid mass thus obtained was recrystallized from suitable solvent to obtain compounds 3a–k.
3-(Benzylidenehydrazono)-5-chloroindolin-2-one (3a)
Yield 82% (ethanol); m. p. 268–270°C. IR (KBr, cm−1): 3246 (NH), 3023 (CH aromatic), 1685 (C=O), 1616 (C=N), 752 (C–Cl); 1H NMR (CDCl3) δ in ppm: 6.8–6.9 (d, 1H, Ar–H), 7.4–7.8 (m, 7H, Ar–H), 8.7 (s, 1H, –N=CH), 11.0 (s, 1H, Het-NH); 13C NMR (CDCl3) δ in ppm: 169.1, 149.5, 145.8, 143.2, 141.1, 138.4, 135.6, 133.7, 130.8, 128.2, 125.9, 123.5, 119.1. Anal. Calcd. for C15H10ClN3O: C 63.50, H 3.55, N 14.81; Found: C 63.57, H 3.47, N 14.89%.
5-Chloro-3-[(2-chlorobenzylidene)hydrazono]indolin-2-one (3b)
Yield 78% (ethanol); m. p. 236–238°C. IR (KBr, cm−1): 3250 (NH), 3064 (CH aromatic), 1703 (C=O), 1617 (C=N), 743 (C–Cl); 1H NMR (CDCl3) δ in ppm: 6.9–7.0 (d, 1H, Ar–H), 7.2–7.4 (m, 5H, Ar–H), 8.25–8.35 (m, 1H, Ar–H), 9.1 (s, 1H, –N=CH), 11.1 (s, 1H, Het-NH); 13C NMR (CDCl3) δ in ppm: 169.0, 151.1, 146.5, 144.2, 142.2, 140.1, 138.0, 136.1, 133.6, 131.8, 129.7, 127.8, 125.5, 123.1, 119.2. Anal. Calcd. for C15H9Cl2N3O: C 56.63, H 2.85, N 13.21; Found: C 56.71, H 2.80, N 13.27%.
5-Chloro-3-[(4-chlorobenzylidene)hydrazono]indolin-2-one (3c)
Yield 85% (ethanol); m. p. 185–187°C. IR (KBr, cm−1): 3280 (NH), 3068 (CH aromatic), 1685 (C=O), 1623 (C=N), 755 (C–Cl); 1H NMR (DMSO-d 6) δ in ppm: 6.9–7.0 (s, 1H, Ar–H), 7.35–7.95 (m, 6H, Ar–H), 8.58 (s, 1H, –N=CH), 11.0 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 169.2, 149.3, 142.2, 140.5, 138.6, 136.5, 134.8, 132.3, 130.6, 129.2, 126.4, 123.9, 118.9. Anal. Calcd. for C15H9Cl2N3O: C 56.63, H 2.85, N 13.21; Found: C 56.75, H 2.79, N 13.24%.
5-Chloro-3-[(3-methoxybenzylidene)hydrazono]indolin-2-one (3d)
Yield 87% (methanol); m. p. 198–200°C. IR (KBr, cm−1): 3242 (NH), 3065 (CH aromatic), 1684 (C=O), 1640 (C=N), 1267 (C–O–C), 745 (C–Cl); 1H NMR (CDCl3) δ in ppm: 3.9 (s, 3H, –OCH 3), 6.85–7.57 (m, 5H, Ar–H), 8.65 (s, 1H, –N=CH), 11.2 (s, 1H, Het-NH); 13C NMR (CDCl3) δ in ppm: 169.4, 160.7, 150.8, 142.2, 139.7, 136.8, 134.5, 131.6, 129.1, 127.0, 124.7, 120.8, 118.2, 116.1, 111.0, 54.9. Anal. Calcd. for C16H12ClN3O2: C 61.25, H 3.86, N 13.39; Found: C 61.33, H 3.75, N 13.34%.
5-chloro-3-[(2-hydroxybenzylidene)hydrazono]indolin-2-one ( 3e ) Khan et al. (2009).
5-Chloro-3-[(4-hydroxybenzylidene)hydrazono]indolin-2-one (3f)
Yield 88% (ethanol); m. p. 238–240°C. IR (KBr, cm−1): 3410 (Ar–OH), 3290 (NH), 3055 (CH aromatic), 1675 (C=O), 1639 (C=N), 751 (C–Cl); 1H NMR (DMSO-d 6) δ in ppm: 6.7–6.8 (d, 1H, Ar–H), 6.8–6.9 (d, 2H, Ar–H), 7.6–7.8 (m, 4H, Ar–H), 8.58 (s, 1H, –N=CH), 10.1 (s, 1H OH), 11.1 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 169.2, 161.0, 149.6, 141.1, 138.1, 134.9, 132.7, 130.8, 127.5, 125.5, 123.0, 119.8, 116.1. Anal. Calcd. for C15H10ClN3O2: C 60.11, H 3.36, N 14.02; Found: C 60.15, H 3.47, N 14.13%.
5-Chloro-3-[(4-dimethylaminobenzylidene)hydrazono]indolin-2-one (3g)
Yield 83% (ethanol); m. p. 228–230°C. IR (KBr, cm−1): 3306 (NH), 3077 (CH aromatic), 2846 (CH aliphatic), 1688 (C=O), 1626 (C=N), 748 (C–Cl); 1H NMR (CDCl3) δ in ppm: 2.4 (s, 6H, –N(CH3)2), 6.7–6.8 (d, 2H, Ar–H), 6.9–7.0 (d, 1H, Ar–H), 7.58–7.8 (m, 4H, Ar–H), 8.6 (s, 1H, –N=CH), 11.1 (s, 1H, Het-NH); 13C NMR (CDCl3) δ in ppm: 169.9, 153.4, 149.4, 140.2, 138.1, 136.0, 133.7, 131.8, 129.5, 125.4, 122.1, 119.3, 111.8, 40.1. Anal. Calcd. for C17H15ClN4O: C 62.48, H 4.63, N 17.15; Found: C 62.55, H 4.52, N 17.20%.
5-Chloro-3-[(4-methoxybenzylidene)hydrazono]indolin-2-one (3h)
Yield 90% (ethanol); m. p. 243–244°C. IR (KBr, cm−1): 3310 (NH), 3061 (CH aromatic), 1695 (C=O), 1625 (C=N), 1251 (C–O–C), 750 (C–Cl); 1H NMR (CDCl3) δ in ppm: 3.85 (s, 3H, –OCH 3 ), 6.79–6.85 (d, 1H, Ar–H), 6.92–7.0 (d, 2H, Ar–H), 7.75–7.98 (m, 4H, Ar–H), 8.6 (s, 1H, –N=CH), 11.2 (s, 1H, Het-NH); 13C NMR (CDCl3) δ in ppm: 169.5, 162.6, 150.2, 142.6, 140.2, 137.7, 135.3, 132.7, 130.0, 127.2, 124.5, 119.6, 114.5, 55.9. Anal. Calcd. for C16H12ClN3O2: C 61.25, H 3.86, N 13.39; Found: C 61.33, H 3.81, N 13.46%.
5-chloro-3-[(4-fluorobenzylidene)hydrazono]indolin-2-one ( 3i ) Khan et al. (2009).
5-Chloro-3-[(4-nitrobenzylidene)hydrazono]indolin-2-one (3j)
Yield 75% (ethanol); m. p. 280°C. IR (KBr, cm−1): 3316 (NH), 3073 (CH aromatic), 1686 (C=O), 1638 (C=N), 1535, 1350 (NO2), 754 (C–Cl); 1H NMR (DMSO-d 6) δ in ppm: 6.85–6.95 (m, 1H, Ar–H), 7.53–7.7 (m, 2H, Ar–H), 8.1 (d, 2H, Ar–H), 8.4 (d, 2H, Ar–H), 8.7 (s, 1H, –N=CH), 11.1 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 169.1, 152.0, 149.7, 142.3, 140.0, 137.9, 134.0, 132.1, 130.1, 128.6, 126.5, 124.3, 119.7. Anal. Calcd. for C15H9ClN4O3: C 54.81, H 2.76, Cl 10.79, N 17.04; Found: C 54.89, H 2.69, N 10.83%.
5-Chloro-3-[(furan-2-ylmethylene)hydrazono]indolin-2-one (3k)
Yield 89% (ethanol); m. p. 265°C. IR (KBr, cm−1): 3300 (NH), 3072 (CH aromatic), 1685 (C=O), 1635 (C=N), 1258 (C–O–C), 753 (C–Cl); 1H NMR (DMSO-d 6) δ in ppm: 6.6 (d, 1H, Ar–H), 6.88–6.96 (m, 1H, Ar–H), 7.2 (d, 1H, Ar–H), 7.68–7.77 (t, 3H, Ar–H), 8.58 (s, 1H, –N=CH), 11.2 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 169.1, 163.9, 149.2, 144.2, 140.9, 137.4, 132.0, 130.0, 127.2, 123.3, 120.2, 118.1, 112.6. Anal. Calcd. for C13H8ClN3O2 : C 57.05, H 2.95, N 15.35; Found: C 57.13, H 2.97, N 15.29%.
General procedure for the synthesis of 3-(5-chloro-2-oxoindolin-3-ylideneamino)-2-arylthiazolidin-4-one (4a–k)
The mixture of 5-chloro-3-[(arylidene)hydrazono] indoline-2-one (3a–k, 0.1 mol) and thioglycolic acid (0.1 mol) in ethanol (100 ml) in presence of anhydrous ZnCl2 (a pinch) was refluxed for 10–12 h on water bath. The reaction mixture was poured into ice-cold water, filtered and finally recrystallized from appropriate solvents to give compounds 4a–k.
3-(5-Chloro-2-oxoindolin-3-ylidendeamino)-2-phenylthiazolidin-4-one (4a)
Yield 69% (methanol); m. p. 124–126°C. IR (KBr, cm−1): 3310 (NH), 3070 (CH aromatic), 1771, 1680 (C=O), 1632 (C=N), 750 (C–Cl), 700 (C–S–C); 1H NMR (DMSO-d 6) δ in ppm: 3.1 (s, 2H, CH 2 of thiazolidinone ring), 4.3 (s, 1H, –N–CH–Ar), 6.9–6.94 (d, 1H, Ar–H), 7.24–7.3 (t, 3H, Ar–H), 7.54–7.66 (m, 2H, Ar–H), 7.86–7.94 (t, 2H, Ar–H), 11.1 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 171.0, 167.7, 146.2, 144.1, 141.6, 139.3, 136.7, 134.6, 132.0, 129.4, 127.1, 124.8, 118.9, 56.5, 35.6. Anal. Calcd. for C17H12ClN3O2S: C 57.06, H 3.38, N 11.74, S 8.96; Found: C 56.97, H 3.43, N 11.66, S 8.88%. MS: [M]+ at m/z 357.81.
3-(5-Chloro-2-oxoindolin-3-ylideneamino)-2-(2-chlorophenyl)thiazolidin-4-one (4b)
Yield 78% (ethanol); m. p. 188–189°C. IR (KBr, cm−1): 3302 (NH), 3080 (CH aromatic), 1762, 1688 (C=O), 1627 (C=N), 750 (C–Cl), 695 (C–S-C); 1H NMR (DMSO-d 6) δ in ppm: 3.22 (s, 2H, CH 2 of thiazolidinone ring), 4.8 (s, 1H, –N–CH–Ar), 6.9–7 (d, 1H, Ar–H), 7.2–7.45 (m, 5H, Ar–H), 8.2–8.35 (m, 1H, Ar–H), 11.1 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 171.3, 167.9, 150.4, 148.9, 145.5, 142.8, 140.3, 137.8, 135.2, 132.8, 130.5, 127.8, 125.6, 119.1, 102.3, 51.2, 35.9. Anal. Calcd. For C17H11Cl2N3O2S: C 52.05, H 2.83, N 10.71, S 8.17; Found: C 52.11, H 2.89, N 10.66, S 8.12%. MS: [M]+ at m/z 392.26.
3-(5-Chloro-2-oxoindolin-3-ylideneamino)-2-(4-chlorophenyl)thiazolidin-4-one (4c)
Yield 66% (chloroform); m. p. 138–140°C. IR (KBr, cm−1): 3306 (NH), 307 6 (CH aromatic), 1760, 1685 (C=O), 1624 (C=N), 745 (C–Cl), 689 (C–S–C); 1H NMR (DMSO-d 6) δ in ppm: 3.2 (s, 2H, CH 2 of thiazolidinone ring), 4.3 (s, 1H, –N–CH–Ar), 6.8–7.0 (d, 1H, Ar–H), 7.35–7.45 (d, 2H, Ar–H), 7.5–7.68 (m, 2H, Ar–H), 7.86–7.95 (d, 2H, Ar–H), 11.0 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 171.2, 168.4, 145.1, 142.4, 140.3, 137.8, 135.6, 133.1, 130.5, 128.0, 125.7, 123.3, 119.1, 56.5, 35.1. Anal. Calcd. for C17H11Cl2N3O2S: C 52.05, H 2.83, N 10.71, S 8.17; Found: C 51.97, H 2.89, N 10.67, S 8.12%. MS: [M]+ at m/z 392.26.
3-(5-Chloro-2-oxoindolin-3-ylideneamino)-2-(3-methoxyphenyl)thiazolidin-4-one (4d)
Yield 74% (ethanol); m. p. 148–150°C. IR (KBr, cm−1): 3315 (NH), 3074 (CH aromatic), 1764, 1682 (C=O), 1615 (C=N), 1250 (C–O–C), 748 (C–Cl), 682 (C–S–C); 1H NMR (DMSO-d 6) δ in ppm: 3.18 (s, 2H, CH 2 of thiazolidinone ring), 3.9 (s, 3H, –OCH 3), 4.62 (s, 1H, –N–CH–Ar), 6.9–6.94 (d, 1H, Ar–H), 7.02–7.06 (d, 2H, Ar–H), 7.22–7.32 (m, 3H, Ar–H), 7.54–7.64 (m, 2H, Ar–H), 11.1 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 171.2, 168.6, 160.3, 141.7, 139.5, 137.0, 134.9, 132.5, 130.2, 127.7, 125.5, 119.8, 117.1, 114.3, 112.1, 58.3, 56.2, 35.7. Anal. Calcd. for C18H14ClN3O3S: C 55.74, H 3.64, N 10.83, S 8.27; Found: C 55.82, H 3.57, N 10.75, S 8.18%. MS: [M]+ at m/z 387.84.
3-(5-Chloro-2-oxoindolin-3-ylideneamino)-2-(2-hydroxyphenyl)thiazolidin-4-one (4e)
Yield 65% (ethanol); m. p. 240–242°C. IR (KBr, cm−1): 3435 (Ar–OH), 3312 (NH), 3075 (CH aromatic), 1763, 1688 (C=O), 1622 (C=N), 750 (C–Cl), 690 (C–S–C); 1H NMR (DMSO-d 6) δ in ppm: 3.3 (s, 2H, CH 2 of thiazolidinone ring), 4.6 (s, 1H, –N–CH–Ar), 6.7–6.9 (d, 1H, Ar–H), 7.03–7.4 (m, 4H, Ar–H), 7.5–7.8 (m, 2H, Ar–H), 11.1 (s, 1H, Het-NH), 11.4 (s, 1H, OH); 13C NMR (DMSO-d 6) δ in ppm: 171.4, 168.1, 153.2, 142.4, 140.0, 137.6, 135.4, 132.9, 130.6, 128.1, 125.7, 122.8, 120.4, 117.9, 115.6, 50.2, 35.6. Anal. Calcd. for C17H12ClN3O3S: C 54.62, H 3.24, N 11.24, S 8.58; Found: C 54.69, H 3.21, N 11.18, S 8.49%. MS: [M]+ at m/z 373.81.
3-(5-Chloro-2-oxoindolin-3-ylideneamino)-2-(4-hydroxyphenyl)thiazolidin-4-one (4f)
Yield 72% (ethanol); m. p. 271–272°C. IR (KBr, cm−1): 3440 (Ar–OH), 3310 (NH), 3078 (CH aromatic), 1764, 1690 (C=O), 1624 (C=N), 751 (C–Cl), 689 (C–S-C); 1H NMR (DMSO-d 6) δ in ppm: 3.3 (s, 2H, CH 2 of thiazolidinone ring), 4.4 (s, 1H, –N–CH–Ar), 6.7–6.9 (m, 3H, Ar–H), 7.56–7.8 (m, 4H, Ar–H), 10.1 (s, 1H, OH), 11.0 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 171.3, 168.5, 156.7, 141.1, 138.9, 136.7, 134.4, 131.9, 129.9, 127.6, 125.3, 119.1, 115.6, 56.9, 35.7. Anal. Calcd. for C17H12ClN3O3S: C 54.62, H 3.24, N 11.24, S 8.58; Found: C 54.58, H 3.16, N 11.18, S 8.47%. MS: [M]+ at m/z 373.81.
3-(5-Chloro-2-oxoindolin-3-ylideneamino)-2-[4-(dimethylamino)phenyl]thiazolidin-4-one (4g)
Yield 75% (dioxan); m. p. 245–247°C. IR (KBr, cm−1): 3304 (NH), 3075 (CH aromatic), 2852 (CH aliphatic), 1765, 1689 (C=O), 1616 (C=N), 749 (C–Cl), 692 (C–S–C); 1H NMR (DMSO-d 6) δ in ppm: 2.4 (s, 6H, –N(CH 3)2), 3.5 (s, 2H, CH 2 of thiazolidinone ring), 4.3 (s, 1H, –N–CH–Ar), 6.7–6.8 (d, 2H, Ar–H), 6.9–7.0 (d, 1H, Ar–H), 7.55–7.93 (m, 4H, Ar–H), 11.1 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 171.4, 168.8, 149.3, 142.9, 140.3, 137.8, 135.3, 132.4, 130.1, 127.5, 125.6, 119.3, 112.7, 56.2, 40.5, 35.6. Anal. Calcd. for C19H17ClN4O2S: C 56.93, H 4.27, N 13.98, S 8.00; Found: C 57.10, H 4.20, N 13.86, S 7.93%. MS: [M]+ at m/z 400.88.
3-(5-Chloro-2-oxoindolin-3-ylideneamino)-2-(4-methoxyphenyl)thiazolidin-4-one (4h)
Yield 70% (toluene); m. p. 324°C. IR (KBr, cm−1): 3315 (NH), 3074 (CH aromatic), 1760, 1688 (C=O), 1627 (C=N), 1248 (C–O–C), 748 (C–Cl), 691 (C–S–C); 1H NMR (DMSO-d 6) δ in ppm: 3.2 (s, 2H, CH 2 of thiazolidinone ring), 3.9 (s, 3H, –OCH 3), 4.6 (s, 1H, –N–CH–Ar), 6.68–6.73 (d, 2H, Ar–H), 6.9–6.94 (d, 1H, Ar–H), 7.44–7.64 (m, 2H, Ar–H), 7.83–7.88 (d, 2H, Ar–H), 11.1 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 171.5, 168.6, 159.3, 145.2, 142.5, 139.4, 137.0, 133.9, 131.3, 129.2, 125.4, 119.5, 114.2, 57.5, 55.0, 35.8. Anal. Calcd. for C18H14ClN3O3S: C 55.74, H 3.64, N 10.83, S 8.27; Found: C 55.79, H 3.59, N 10.77%. MS: [M]+ at m/z 387.84.
3-(5-Chloro-2-oxoindolin-3-ylideneamino)-2-(4-fluorophenyl)thiazolidin-4-one (4i)
Yield 67% (benzene); m. p. 176–178°C. IR (KBr, cm−1): 3310 (NH), 3080 (CH aromatic), 1762, 1690 (C=O), 1626 (C=N), 1150 (C–F), 750 (C–Cl), 690 (C–S–C); 1H NMR (DMSO-d 6) δ in ppm: 3.2 (s, 2H, CH 2 of thiazolidinone ring), 4.6 (s, 1H, –N–CH–Ar), 6.8–7.0 (d, 1H, Ar–H), 7.25–7.38 (d, 2H, Ar–H), 7.49–7.7 (m, 2H, Ar–H), 7.85–7.98 (m, 2H, Ar–H), 11.1 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 171.1, 168.7, 161.3, 141.5, 139.2, 136.8, 134.4, 132.3, 129.9, 127.5, 125.2, 119.4, 115.2, 56.3, 36.1. Anal. Calcd. for C17H11ClFN3O2S: C 54.33, H 2.95, N 11.18, S 8.53; Found: C 54.41, H 3.10, N 11.09, S 8.45%. MS: [M]+ at m/z 374.5.
3-(5-Chloro-2-oxoindolin-3-ylideneamino)-2-(4-nitrophenyl)thiazolidin-4-one (4j)
Yield 57% (benzene); m. p. 196–198°C. IR (KBr, cm−1): 3310 (NH), 3075 (CH aromatic), 1762, 1685 (C=O), 1627 (C=N), 1540, 1346 (NO2), 748 (C–Cl), 690 (C–S–C); 1H NMR (DMSO-d 6) δ in ppm: 3.2 (s, 2H, CH 2 of thiazolidinone ring), 4.4 (s, 1H, –N–CH–Ar), 6.8–7.0 (m, 1H, Ar–H), 7.5–7.7 (m, 2H, Ar–H), 8.0–8.25 (d, 2H, Ar–H), 8.75–8.92 (d, 2H, Ar–H), 11.1 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 170.7, 168.3, 147.6, 145.3, 139.4, 137.1, 134.9, 132.6, 130.4, 128.3, 126.0, 123.6, 119.1, 56.7, 35.8. Anal. Calcd. for C17H11ClN4O4S: C 50.69, H 2.75, N 13.91, S 7.96; Found: C 50.74, H 2.67, N 13.83, S 7.89%. MS: [M]+ at m/z 402.81.
3-(5-Chloro-2-oxoindolin-3-ylideneamino)-2-(furan-2-yl)thiazolidin-4-one (4k)
Yield 63% (methanol); m. p. 310°C. IR (KBr, cm−1): 3308 (NH), 3080 (CH aromatic), 1760, 1690 (C=O), 1624 (C=N), 1250 (C–O–C), 750 (C–Cl), 692 (C–S–C); 1H NMR (DMSO-d 6) δ in ppm: 3.3 (s, 2H, CH 2 of thiazolidinone ring), 4.52 (s, 1H, –N–CH–Ar), 6.5–6.7 (d, 1H, Ar–H), 6.85–6.98 (m, 1H, Ar–H), 7.15–7.28 (d, 1H, Ar–H), 7.68–7.78 (t, 3H, Ar–H), 11.2 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 171.4, 168.9, 151.5, 141.7, 139.3, 136.9, 134.4, 131.9, 129.6, 125.5, 119.5, 109.6, 107.2, 55.8, 33.6. Anal. Calcd. for C15H10ClN3O3S: C 51.80, H 2.90, N 12.08, S 9.22; Found: C 51.91, H 2.96, N 11.98, S 9.12%. MS: [M]+ at m/z 347.78.
General procedure for the preparation of 5-chloro-3-(3-chloro-2-oxo-4-arylazetidin-1-ylimino)indolin-2-one (5a–k)
To a stirred solution of 5-chloro-3-[(arylidene)hydrazono] indoline-2-one (3a–k, 0.1 mol) in dioxan (100 ml), chloroacetylchloride (0.1 mol) was added dropwise at 0–5°C temperature in presence of triethylamine. The reaction mixture was stirred for about 8 h and the precipitate of amine hydrochloride was filtered off. The excess of dioxan was distilled off. The mass thus obtained was cooled, poured in ice-cold water, filtered, washed, dried and recrystallized from appropriate solvents to furnish compounds 5a–k.
5-Chloro-3-(3-chloro-2-oxo-4-pheylazetidin-1-ylimino)indolin-2-one (5a)
Yield 85% (ethanol); m. p. 140–142°C. IR (KBr, cm−1): 3315 (NH), 3080 (CH aromatic), 1745, 1720 (C=O), 1625 (C=N), 740 (C–Cl); 1H NMR (DMSO-d 6) δ in ppm: 4.6 (s, 1H, CHCl), 5.2 (s, 1H, –N–CHAr), 6.9–6.94 (d, 1H, Ar–H), 7.18–7.24 (t, 3H, Ar–H), 7.4–7.5 (m, 2H, Ar–H), 7.8–7.86 (t, 2H, Ar–H), 11.1 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 169.3, 166.5, 144.1, 140.0, 138.0, 136.1, 134.2, 132.4, 130.6, 128.9, 127.1, 125.3, 119.6, 64.5, 61.4. Anal. Calcd. for C17H11Cl2N3O2: C 56.69, H 3.08, N 11.67; Found: C 56.77, H 2.98, N 11.58%. MS: [M]+ at m/z 359.00.
5-Chloro-3-[3-chloro-2-(2-chlorophenyl)-4-oxazetidin-1-ylimino]indolin-2-one (5b)
Yield 76% (ethanol); m. p. 120°C. IR (KBr, cm−1): 3312 (NH), 3078 (CH aromatic), 1760, 1728 (C=O), 1622 (C=N), 744 (C–Cl); 1H NMR (DMSO-d 6) δ in ppm: 4.25 (s, 1H, CHCl), 5.2 (s, 1H, –N–CHAr), 6.8–7.0 (d, 1H, Ar–H), 7.15–7.4 (m, 5H, Ar–H), 7.95–8.05 (m, 1H, Ar–H), 11.1 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 168.2, 165.5, 146.2, 144.7, 142.5, 140.9, 139.0, 136,8, 135.1, 133.0, 131.4, 129.5, 127.2, 125.3, 119.1, 63.8, 56.2. Anal. Calcd. for C17H10Cl3N3O2: C 51.74, H 2.55, N 10.65; Found: C 51.81, H 2.59, N 10.74%. MS: [M]+ at m/z 392.98.
5-Chloro-3-[3-chloro-2-(4-chlorophenyl)-4-oxoazetidin-1-ylimino]indolin-2-one (5c)
Yield 82% (ethanol); m. p. 170–172°C. IR (KBr, cm−1): 3309 (NH), 3075 (CH aromatic), 1750, 1720 (C=O), 1626 (C=N), 750 (C–Cl); 1H NMR (DMSO-d 6) δ in ppm: 4.38 (s, 1H, CHCl), 5.4 (s, 1H, –N–CHAr), 6.9–7.0 (d, 1H, Ar–H), 7.2–7.3 (d, 2H, Ar–H), 7.35–7.5 (m, 2H, Ar–H), 7.7–7.8 (d, 2H, Ar–H), 11.0 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 168.0, 166.2, 142.3, 140.4, 138.0, 136.3, 134.4, 132.2, 130.2, 128.1, 126.2, 124.2, 119.1, 64.5, 61.3. Anal. Calcd. For C17H10Cl3N3O2: C 51.74, H 2.55, N 10.65; Found: C 51.83, H 2.48, N 10.57%. MS: [M]+ at m/z 392.98.
5-Chloro-3-[3-chloro-2-(3-methoxyphenyl)-4-oxoazetidin-1-ylimino]indolin-2-one (5d)
Yield 80% (ethanol); m. p. 138°C. IR (KBr, cm−1): 3312 (NH), 3078 (CH aromatic), 1753, 1721 (C=O), 1618 (C=N), 1252 (C–O–C), 749 (C–Cl); 1H NMR (DMSO-d 6) δ in ppm: 3.9 (s, 3H, –OCH 3), 4.8 (s, 1H, CHCl), 5.2 (s, 1H, –N–CHAr), 6.98–7.2 (d, 1H, Ar–H), 7.1–7.14 (d, 1H, Ar–H), 7.3–7.4 (m, 3H, Ar–H), 7.62–7.72 (m, 2H, Ar–H), 11.1 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 168.7, 166.5, 160.6, 144.7, 139.3, 134.2, 132.3, 130.2, 128.6, 126.8, 124.9, 121.1, 119.2, 113.9, 112.0, 64.5, 61.7, 55.6. Anal. Calcd. for C18H13Cl2N3O3: C 55.40, H 3.36, N 10.77; Found: C 55.49, H 3.31, N 10.68%. MS: [M]+ at m/z 390.22.
5-Chloro-3-[3-chloro-2-(2-hydroxyphenyl)-4-oxoazetidin-1-ylimino]indolin-2-one (5e)
Yield 75% (dioxan); m. p. 109°C. IR (KBr, cm−1): 3430 (Ar–OH), 3310 (NH), 3075 (CH aromatic), 1748, 1726 (C=O), 1624 (C=N), 746 (C–Cl); 1H NMR (DMSO-d 6) δ in ppm: 4.8 (s, 1H, CHCl), 5.5 (s, 1H, –N–CHAr), 6.96–7.2 (d, 1H, Ar–H), 7.22–7.3 (m, 4H, Ar–H), 7.62–7.72 (m, 2H, Ar–H), 11.1 (s, 1H, Het-NH), 11.5 (s, 1H, OH); 13C NMR (DMSO-d 6) δ in ppm: 168.0, 166.1, 154.2, 140.8, 138.4, 136.5, 134.6, 132.7, 130.9, 129.0, 127.1, 125.2, 121.2, 119.3, 115.5, 64.8, 55.2. Anal. Calcd. for C17H11Cl2N3O3: C 54.28, H 2.95, N 11.17; Found: C 54.36, H 3.10, N 11.06%. MS: [M]+ at m/z 376.19.
5-Chloro-3-[3-chloro-2-(4-hydroxyphenyl)-4-oxoazetidin-1-ylimino]indolin-2-one (5f)
Yield 84% (chloroform); m. p. 160–162°C. IR (KBr, cm−1): 3438 (Ar–OH), 3315 (NH), 3080 (CH aromatic), 1759, 1720 (C=O), 1620 (C=N), 752 (C–Cl); 1H NMR (DMSO-d 6) δ in ppm: 4.8 (s, 1H, CHCl), 5.4 (s, 1H, –N–CHAr), 6.98–7.1 (d, 1H, Ar–H), 7.1–7.2 (d, 2H, Ar–H), 7.4–7.65 (m, 4H, Ar–H), 10.1 (s, 1H, OH), 11.0 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 168.3, 166.0, 156.7, 139.4, 135.2, 133.2, 131.3, 129.9, 128.3, 126.7, 125.1, 119.2, 115.8, 64.6, 61.2. Anal. Calcd. for C17H11Cl2N3O3: C 54.28, H 2.95, N 11.17; Found: C 54.36, H 3.04, N 11.09%. MS: [M]+ at m/z 376.19.
5-Chloro-3-[3-chloro-2-{4-(dimethylamino)phenyl}-4-oxoazetidin-1-ylimino]indolin-2-one (5g)
Yield 78% (ethylacetate); m. p. 149–150°C. IR (KBr, cm−1): 3308 (NH), 3082 (CH aromatic), 2860 (CH aliphatic), 1750, 1722 (C=O), 1620 (C=N), 748 (C–Cl); 1H NMR (DMSO-d 6) δ in ppm: 2.4 (s, 6H, –N(CH 3)2), 4.8 (s, 1H, CHCl), 5.3 (s, 1H, –N–CHAr), 6.75–6.85 (d, 2H, Ar–H), 6.9–7.1 (d, 1H, Ar–H), 7.7–8.0 (m, 4H, Ar–H), 11.0 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 168.8, 166.3, 149.2, 139.0, 136.0, 133.7, 131.8, 129.5, 127.2, 125.1, 119.3, 112.4, 64.1, 61.6, 40.5. Anal. Calcd. for C19H16Cl2N4O2: C 56.59, H 4.00, N 13.89; Found: C 56.66, H 3.95, N 13.81%. MS: [M]+ at m/z 403.26.
5-Chloro-3-[3-chloro-2-(4-methoxyphenyl)-4-oxoazetidin-1-ylimino]indolin-2-one (5h)
Yield 87% (ethanol); m. p. 112°C. IR (KBr, cm−1): 3310 (NH), 3080 (CH aromatic), 1747, 1721 (C=O), 1625 (C=N), 1250 (C–O–C), 750 (C–Cl); 1H NMR (DMSO-d 6) δ in ppm: 3.85 (s, 3H, –OCH 3), 4.6 (s, 1H, CHCl), 5.42 (s, 1H, –N–CHAr), 6.68–6.74 (d, 2H, Ar–H), 6.9–6.94 (d, 1H, Ar–H), 7.38–7.48 (m, 2H, Ar–H), 7.66–7.72 (d, 2H, Ar–H), 11.1 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 168.0, 166.1, 158.4, 139.5, 136.6, 134.7, 133.0, 131.1, 129.1, 127.2, 125.3, 119.5, 114.0, 64.8, 61.4, 55.5. Anal. Calcd. for C18H13Cl2N3O3: C 55.40, H 3.36, N 10.77; Found: C 55.49, H 3.42, N 10.69%. MS: [M]+ at m/z 390.22.
5-Chloro-3-[3-chloro-2-(4-fluorophenyl)-4-oxoazetidin-1-ylimino]indolin-2-one (5i)
Yield 76% (benzene); m. p. 154°C. IR (KBr, cm−1): 3313 (NH), 3078 (CH aromatic), 1752, 1720 (C=O), 1620 (C=N), 1140 (C–F), 740 (C–Cl); 1H NMR (DMSO-d 6) δ in ppm: 4.78 (s, 1H, CHCl), 5.19 (s, 1H, –N–CHAr), 6.95–7.05 (d, 1H, Ar–H), 7.25–7.35 (t, 2H, Ar–H), 7.5–7.7 (m, 2H, Ar–H), 7.85–7.95 (m, 2H, Ar–H), 11.0 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 168.4, 166.1, 161.0, 141.4, 139.3, 133.9, 132.0, 130.1, 128.0, 126.3, 124.2, 119.1, 115.5, 64.4, 61.2. Anal. Calcd. for C17H10Cl2FN3O2: C 53.99, H 2.67, N 11.11; Found: C 54.08, H 2.59, N 11.04%. MS: [M]+ at m/z 378.18.
5-Chloro-3-[3-chloro-2-(4-nitrophenyl)-4-oxoazetidin-1-ylimino]indolin-2-one (5j)
Yield 81% (toluene); m. p. 212°C. IR (KBr, cm−1): 3315 (NH), 3082 (CH aromatic), 1759, 1728 (C=O), 1625 (C=N), 1544, 1348 (NO2), 742 (C–Cl); 1H NMR (DMSO-d 6) δ in ppm: 4.9 (s, 1H, CHCl), 5.19 (s, 1H, –N–CHAr), 6.95–7.08 (m, 1H, Ar–H), 7.65–7.8 (m, 2H, Ar–H), 8.05–8.15 (d, 2H, Ar–H), 8.35–8.5 (d, 2H, Ar–H), 11.0 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 168.2, 166.1, 149.6, 145.8, 139.5, 133.7, 131.6, 129.5, 127.6, 125.5, 123.5, 121.7, 119.2, 64.0, 61.5. Anal. Calcd. for C17H10Cl2N4O4: C 50.39, H 2.49, N 13.83; Found: C 50.48, H 2.41, N 13.74%. MS: [M]+ at m/z 405.19.
5-Chloro-3-[3-chloro-2-(furan-2-yl)-4-oxoazetidin-1-ylimino]indolin-2-one (5k)
Yield 85% (methanol); m. p. 102°C. IR (KBr, cm−1): 3312 (NH), 3080 (CH aromatic), 1760, 1725 (C=O), 1620 (C=N), 1253 (C–O–C), 746 (C–Cl); 1H NMR (DMSO-d 6) δ in ppm: 4.7 (s, 1H, CHCl), 5.18 (s, 1H, –N–CHAr), 6.7–6.9 (d, 1H, Ar–H), 6.95–7.1 (m, 1H, Ar–H), 7.25–7.4 (d, 1H, Ar–H), 7.75–7.9 (t, 3H, Ar–H), 11.1 (s, 1H, Het-NH); 13C NMR (DMSO-d 6) δ in ppm: 168.4, 166.3, 151.1, 141.6, 139.5, 134.7, 132.6, 130.8, 128.9, 125.2, 119.1, 111.3, 109.1, 62.2, 59.3. Anal. Calcd. for C15H9Cl2N3O3: C 51.45, H 2.59, N 12.00; Found: C 51.56, H 2.48, N 11.94%. MS: [M]+ at m/z 350.16.
Antibacterial and antifungal activity (MIC)
The bacterial and fungal strains were procured from National Chemical Laboratory (NCL), Pune, India. The antibacterial activity of the synthesized compounds was screened against the following bacterial strains: Bacillus subtilis ATCC 6633, Staphylococcus epidermidis ATCC 12228, Micrococcus luteus ATCC 4698, Staphylococcus aureus ATCC 25923, Staphylococcus hominis ATCC 27844, Bacillus pumilus ATCC 14884, Bacillus cereus ATCC 11778, Proteus vulgaris ATCC 13315, Proteus mirabilis ATCC 49565, Salmonella typhi ATCC 19430, Klebsiella pneumonia ATCC 13883, Escherichia coli ATCC 25922 and Pseudomonas aeroginosa ATCC 10145.
The compounds were also screened against the following fungal strains: Aspergillus niger ATCC 9142, Aspergillus awamori ATCC 22342, Candida albicans ATCC 10231, Alternaria alternate ATCC 66868, Microsporum canis ATCC 11622, Rhizoctonia solani ATCC 76131, Trichophyton longiformis ATCC 22397, Aspergillus flavus ATCC 15517, Fusarium solani ATCC 38136 and Trichoderma viride ATCC 52440.
The MIC was done by broth dilution method. Nutrient broth and potato dextrose broth was procured from Himedia Laboratories. A set of sterilized test tubes with nutrient broth medium capped with cotton plugs were taken (1–12). The test compounds were dissolved in suitable solvent (DMF) and at the concentration of 600 μg ml−1, which were serially diluted from 1 to 12. A fixed volume of 0.5 ml culture was added in all the test tubes and was incubated at 37°C for 24 h. After 24 h, tubes were observed visually for turbidity.
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Acknowledgment
Sunil G. Shingade is thankful to UGC New Delhi, India for the award of J. R. F.—Rajiv Gandhi National Junior Research Fellowship and financial support for this work.
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Shingade, S.G., Bari, S.B. & Waghmare, U.B. Synthesis and antimicrobial activity of 5-chloroindoline-2,3-dione derivatives. Med Chem Res 21, 1302–1312 (2012). https://doi.org/10.1007/s00044-011-9644-y
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DOI: https://doi.org/10.1007/s00044-011-9644-y