Synthesis and evaluation of functionalized indoles as antimycobacterial and anticancer agents.
A new series of 5-fluoro-N(2)-(cyclohexylidene)-3-phenyl-1H-indole-2-carbohydrazides (6a-6e) and their cyclization products 5-fluoro-N-(3-oxo-1-thia-4-azaspiro [4.5]dec-4-yl)-3-phenyl-1H-indole-2-carboxamides (7a-7e, 8a-8e) have been synthesized and evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv using the Microplate Alamar Blue Assay (MABA). Compounds showed moderate to good inhibitory activity at 6.25 μg/mL. Among them, 7b, 7d, 8b, and 8d were the most potent analogs with an inhibition range of 91-95 %. Additionally, compounds 6a, 7a, 7e, 8a, and 8e were subjected to the National Cancer Institute's (NCI) in vitro disease-oriented antitumor screening to be evaluated for antitumor activity. 8e, the most potent compound examined, displayed broad spectrum antiproliferative activity with particular selectivity against four leukemia cell lines (CCRF-CEM, HL-60 (TB), K-562, and RPMI-8226) with log                         (10)                         GI                         (50) values between -5.68 and -6.09.
Department of Pharmaceutical Chemistry, Istanbul University, Beyazıt 34116, Istanbul, Turkey. gokcechn@istanbul.edu.tr
Gökçe
G
Cihan-Üstündağ
Gültaze
G
Capan
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D002522:Chlorocebus aethiops; D003500:Cyclization; D006801:Humans; D006835:Hydrazones / Q000737:chemistry; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D014709:Vero Cells
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D006835:Hydrazones; D007211:Indoles