Synthesis and pharmacological evaluation of combretastatin-A4 analogs of pyrazoline and pyridine derivatives as anticancer, anti-inflammatory and antioxidant agents

Abstract

Three category of N1-phenyl pyrazoline (5a–e), N1-phenyl-sulfonyl pyrazoline (6a–e), and pyridine analogs (8a–d) of combretastatin-A4 were synthesized. The structures of compounds were verified by spectroscopic techniques. All the compounds were screened for their anticancer activity against MCF-7 cell line, antioxidant (DPPH, NO, SOR and H2O2), and anti-inflammatory activity while compounds (8a–d) additionally tested against K562 cell line. Compounds 8a and 8b showed substantial anticancer activity against MCF-7 cell line (GI50 = 5.59 and 11.70 µM), although not comparable with adriamycin (GI50 ⩽ 0.1 µM). However, none of the compound was active against the K562 cell line. Nevertheless, compound 8a displayed better cytostatic activity (TGI = 69.2 µM) than the standard drug adriamycin (TGI = 75.8 µM). Most of the compounds 5a, 5b, 5c, 5e, 6a, 6b, 6c, 6d, 6e 8a, and 8b have excellently inhibited all of the free radicals better than standard drug ascorbic acid, whereas compound 5c and 5b demonstrated significant anti-inflammatory activity comparable with diclofenac sodium, a standard anti-inflammatory drug.