ABSTRACT
Two different series of novel analogues of benzosuberones (5a-m and 9a-w) tethered with hydrazone-hydrazides (functional group alterations: Head group to Tail group and vice versa) have been synthesized by the reaction of appropriate aldehydes with substituted hydrazides in excellent yields (87-94%) and their structures were confirmed by (1)H NMR, (13)C NMR, ESI-MS and HRMS. The newly synthesized compounds were evaluated for anti-proliferative activity against different human cancer cell lines (HeLa, MDA MB 231, MIAPACA and IMR32). Among the synthesized compounds, six compounds 5 a, 5 b, 5 d, 5 e, 5 f and 9 v exhibited potent anti-proliferative activity with GI50 values less than 0.01 µM against MIAPACA, MDA-MB-231 and IMR32 human cancer cell lines.
Subject(s)
Antineoplastic Agents/chemical synthesis , Coumarins/chemistry , Drug Design , Hydrazines/chemistry , Hydrazones/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Coumarins/chemical synthesis , Coumarins/pharmacology , HeLa Cells , Humans , Structure-Activity RelationshipABSTRACT
A series of novel benzosuberone bearing coumarin moieties 5a-c have been synthesized and their structures were determined by analytical and spectral (FT-IR, (1)H NMR, (13)C NMR, HRMS) studies. The newly synthesized compounds were evaluated for their cytotoxicity against four human cancer cell lines, A549 (Human alveolar adenocarcinoma cell line), HeLa (Human cervical cancer cell line), MDA-MB-231 (Human breast adenocarcinoma cell line), MCF-7 (Human breast adenocarcinoma cell line) and normal cell line HEK293 (Human embryonic kidney cell line). Compound 5a exhibited promising cytotoxicity with IC50 values ranging from 3.35 to 16.79 µM against all the cancer cell lines like A549, HeLa, MCF-7 and MDA-MB-231, while compound 5c showed significant cytotoxicity against HeLa and MDA-MB-231 with IC50 values of 6.72 and 4.87, respectively.
