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

Three category of N 1 -phenyl pyrazoline ( 5a – e ), N 1 -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 H 2 O 2 ), 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 (GI 50 = 5.59 and 11.70 µM), although not comparable with adriamycin (GI 50 ⩽ 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.