Department of Chemistry
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Item Synthesis and anticancer activity of 5-(3-indolyl)-1,3,4-thiadiazoles(Elsiever, 2010-10) Kumar, DalipA series of 5-(3-indolyl)-2-substituted-1,3,4-thiadiazoles 5a–m were synthesized and their cytotoxicity analyzed against six human cancer cell lines. The reaction of indole-3-carboxylic acid 3 with aryl or heteroaryl hydrazides afforded the N,N′-diacylhydrazines 4, which upon treatment with Lawesson’s reagent resulted in the formation of indolyl-1,3,4-thiadiazoles 5a–m in good yields. Indolyl-1,3,4-thiadiazole 5m with 4-benzyloxy-3-methoxyphenyl and 5-bromo indolyl substituents is the most active in suppressing the growth of cancer cells (IC50 1.5 μM, PaCa2). The compounds 5b, 5e and 5h bearing C-2 substituent as benzyl, 3,4-dimethoxyphenyl and 4-benzyloxy-3-methoxyphenyl, respectively, have shown significant cytotoxicity against multiple cancer cell lines. Introduction of 4-dimethylamino (5d and 5k) and 3,4,5-trimethoxy (5l) groups in the C-2 phenyl ring induced selectivity against MCF7 and MDA-MB-231 cancer cell lines (compounds 5d, 5k and 5l).Item Synthesis and anticancer activity of 5-(3-indolyl)-1,3,4-thiadiazoles(Elsiever, 2010-10) Kumar, DalipA series of 5-(3-indolyl)-2-substituted-1,3,4-thiadiazoles 5a–m were synthesized and their cytotoxicity analyzed against six human cancer cell lines. The reaction of indole-3-carboxylic acid 3 with aryl or heteroaryl hydrazides afforded the N,N′-diacylhydrazines 4, which upon treatment with Lawesson’s reagent resulted in the formation of indolyl-1,3,4-thiadiazoles 5a–m in good yields. Indolyl-1,3,4-thiadiazole 5m with 4-benzyloxy-3-methoxyphenyl and 5-bromo indolyl substituents is the most active in suppressing the growth of cancer cells (IC50 1.5 μM, PaCa2). The compounds 5b, 5e and 5h bearing C-2 substituent as benzyl, 3,4-dimethoxyphenyl and 4-benzyloxy-3-methoxyphenyl, respectively, have shown significant cytotoxicity against multiple cancer cell lines. Introduction of 4-dimethylamino (5d and 5k) and 3,4,5-trimethoxy (5l) groups in the C-2 phenyl ring induced selectivity against MCF7 and MDA-MB-231 cancer cell lines (compounds 5d, 5k and 5l).Item Synthesis and biological evaluation of indolyl chalcones as antitumor agents(Elsiever, 2010-07) Kumar, DalipA series of indolyl chalcones were synthesized and evaluated in vitro for their anticancer activity against three human cancer cell lines. Compounds 3b–d, 3h, 3j, 3l, 3m, 4g, and 4j showed significant cytotoxicity, particularly, indolyl chalcones 3l and 3m were identified as the most potent and selective anticancer agents with IC50 values 0.03 and 0.09 μM, against PaCa-2 cell line, respectively.Item Synthesis of novel indolyl-1,2,4-triazoles as potent and selective anticancer agents(Wiley, 2010-12) Kumar, DalipA diverse series of 22 indolyl-1,2,4-triazole congeners (6 and 7) have been synthesized from the reaction of indole-3-carbonitrile (4) or (5) with appropriate acid hydrazides in the presence of potassium carbonate. Synthesized compounds were evaluated for their cytotoxicity against six human cancer cell lines, and some of the compounds displayed promising activity. In particular, 3-(3′,4′,5′-trimethoxyphenyl)-5-(N-methyl-3′-indolyl)-1,2,4-triazole (7i) and 3-(4′-piperidinyl)-5-(N-methyl-3′-indolyl)-1,2,4-triazole (7n) were the most promising and broadly active compounds against the tested cell lines. It was interesting to note that the trimethoxyphenyl analog 7i showed twofold selective cytotoxicity against PaCa2 cell line (IC50 0.8 μm), whereas piperidinyl analog 7n was found to be selectively cytotoxic against MCF7 cell line (IC50 1.6 μm). Notably, the 4-fluorophenyl derivative 7c exhibited selective cytotoxicity against PC3 cell line (IC50 4 μm). The structure–activity relationship study revealed that substituents including 3,4,5-trimethoxyphenyl, 3,4-dimethoxyphenyl, 4-benzyloxy-3-methoxyphenyl, 4-piperidinyl, 4-fluorophenyl and N-methylindole are beneficial for the activity of indolyl-1,2,4-triazoles (6 and 7).Item One-pot synthesis and anticancer studies of 2-arylamino-5-aryl-1,3,4-thiadiazoles(Elsiever, 2011-04) Kumar, DalipA series of 2-arylamino-5-aryl-1,3,4-thiadiazoles 1a–j were synthesized and screened for their anticancer activity against various human cancer cell lines. The novel one-pot synthesis of 1,3,4-thiadiazoles was achieved by refluxing aryl aldehydes, hydrazine hydrate, and aryl isothiocyanates in methanol followed by oxidative cyclization with ferric ammonium sulfate. The compounds 1g–j with trimethoxyphenyl at the C-5 position displayed extremely potent anticancer activity with at least twofold selectivity (IC50: 4.3–9.2 μM). The nature of substituent on the C-2 arylamino ring may be critical in opting for the selectivity towards a particular cancer cell.Item Synthesis and in-vitro anticancer activity of 3,5-bis(indolyl)-1,2,4-thiadiazoles(Elsiever, 2011-10) Kumar, DalipA series of 3,5-bis(indolyl)-1,2,4-thiadiazoles were synthesized and evaluated for their cytotoxicity against selected human cancer cell lines. The reaction of indole-3-thiocarboxamide 3 with iodobenzene diacetate underwent oxidative dimerization to give 3,5-bis(indolyl)-1,2,4-thiadiazoles 4a–n. Among the synthesized bis(indoly)-1,2,4-thiadiazoles, the compound 4h with 4-chlorobenzyl and methoxy substituents showed the most potent activity.Item Synthesis of novel 1,2,4-oxadiazoles and analogues as potential anticancer agents(Elsiever, 2011-07) Kumar, DalipA library of 3,5-disubstituted-1,2,4-oxadiazoles 7–9 and their bioisosters, 1,3,4-oxadiazole 14 and 1,3,4-thiadiazole 16, were synthesized and evaluated in vitro for their anticancer potential against a panel of six human cancer cell lines. The key step in the synthesis of oxadiazoles 7–9 involve coupling of amidoxime 6 with an appropriate carboxylic acid followed by thermal cyclization. The bioisosteres, 1,3,4-oxadiazole 14 and 1,3,4-thiadiazole 16 were prepared from the reaction of a common precursor diacylhydrazine 13 with thionyl chloride and Lawesson′s reagent, respectively. The anticancer studies on the synthesized compounds revealed that presence of a cyclopentyloxy or n-butyloxy on the C-3 aryl ring and piperdin-4-yl or trichloromethyl at the C-5 position of 1,2,4-oxadiazole is essential for good activity. In particular, 1,2,4-oxadiazole 7i and analogue 1,3,4-thiadiazole 16 exhibited significant activity against DU145 (IC50: 9.3 μM) and MDA-MB-231 (IC50: 9.2 μM) cell lines, respectively.Item Novel bis(indolyl)hydrazide–hydrazones as potent cytotoxic agents(Elsiever, 2012-01) Kumar, DalipA series of bis(indolyl) hydrazide–hydrazones 5a–n were synthesized and evaluated for their cytotoxicity against selected human cancer cell lines. The reaction of indole-3-carboxaldehyde 2 with indole-3-carbohydrazide 4 in presence of catalytic amount of acetic acid afforded 5a–n in good yields. Among the synthesized bis(indolyl)hydrazide–hydrazones, the compound 5b with N-(p-chlorobenzyl) and bromo substituents was found to be the most potent against multiple cancer cell lines (IC50 = 1.0 μM, MDA-MB-231). The compound 5k exhibited selective cytotoxicity against breast cancer cell line MCF7 (IC50 = 3.1 μM).