ABSTRACT
Microwave-assisted synthesis of 23 α-cyano bis(indolyl)chalcones (6a-w) and their in vitro anticancer activity against three human cancer cell lines have been discussed. Among the synthesized chalcones, compound 6n was found to be the most potent and selective against A549 lung cancer cell line (IC50 = 0.8 µM). In a preliminary mechanism of action studies some α-cyano bis(indolyl)chalcones were found to enhance tubulin polymerization suggesting these compounds could act as microtubule stabilizing agents.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Chalcones/chemical synthesis , Chalcones/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/physiology , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor/methods , HumansABSTRACT
A recipe for potency: A novel series of bis(indolyl)-1,3,4-oxadiazoles was prepared from the corresponding hydrazide-hydrazones via iodobenzene diacetate-promoted oxidative cyclization. Evaluation against a panel of human cancer cell lines revealed that some derivatives possess potent cytotoxicity with tunable selectivity for different cancer types.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Oxadiazoles/chemical synthesis , Oxadiazoles/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cytotoxins/chemical synthesis , Cytotoxins/chemistry , Cytotoxins/pharmacology , Drug Screening Assays, Antitumor , Humans , Indoles/chemical synthesis , Indoles/chemistry , Indoles/pharmacology , Neoplasms/drug therapy , Oxadiazoles/chemistryABSTRACT
A 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 (IC(50)=1.0 µM, MDA-MB-231). The compound 5k exhibited selective cytotoxicity against breast cancer cell line MCF7 (IC(50)=3.1 µM).
Subject(s)
Antineoplastic Agents/pharmacology , Chemistry, Pharmaceutical/methods , Hydrazines/chemistry , Hydrazones/chemistry , Indoles/chemistry , Neoplasms/drug therapy , Acetic Acid/chemistry , Animals , Catalysis , Cell Line, Tumor , Drug Design , Drug Screening Assays, Antitumor/methods , Humans , Hydrazines/pharmacology , Hydrazones/pharmacology , Inhibitory Concentration 50 , Models, Chemical , PoriferaABSTRACT
A 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 (IC(50) 1.5 muM, 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).