Synthesis of novel 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole derivatives as antiproliferative agents: A structure–activity relationship study
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A series of novel 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole derivatives 5(a–m) were synthesized with different substituted aromatic/heterocyclic acid chlorides (R-CO-Cl) and characterized by 1H NMR, LC/MS, FTIR and elemental analyses. All the compounds synthesised were evaluated for their antiproliferative activity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The antiproliferative effects of the synthesised compounds were tested against viable human skin fibroblast cells and carcinoma cells namely HeLa cells, HT-29 cells, MCF-7 cells, HepG-2 cells by adopting positive and negative control. The importance of the aromatic and heterocyclic moiety was confirmed. From the SAR studies, it reveals that, the substitution at N-terminal of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole by the heterocyclic ring plays a dominant role and was responsible for the antiproliferative activity. Among the synthesized compounds 5a, 5d and 5k have showed potent antiproliferative activity on all the carcinoma cells tested.
KeywordsIsonipecotic acid 6-fluoro-3-(4-piperidinyl)-1 2-benzisoxazole Acid chloride MTT assay Antiproliferative activity Cancer therapy Cell proliferation.
The authors are grateful to Council of Scientific and Industrial Research (CSIR), New Delhi for financial support under the project 01(1904)/03/EMR-II 2004, CSIR-SRF to K. Vinaya order No. 09/119(0172)2K8 EMR-I, Elemental Analysis and IR spectroscopic data were obtained from instruments funded by DST-FIST and UGC-SAP (phase I) No.F.540/10/DRS/2004-05 (SAP-I) is greatly acknowledged.
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