Synthesis and anticancer activity of 5-(3-indolyl)-1,3,4-thiadiazoles.
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).
Kumar
Dalip
D
Chemistry Group, Birla Institute of Technology and Science, Pilani, Rajasthan 333 031, India. dalipk@bits-pilani.ac.in
Maruthi Kumar
N
N
Chang
Kuei-Hua
KH
Shah
Kavita
K
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D011471:Prostatic Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D007211:Indoles; D013830:Thiadiazoles; C058949:1,3,4-thiadiazole