Synthesis and Pharmacological Evaluation of Pyrazoline and Pyrimidine Analogs of Combretastatin-A4 as Anticancer, Anti-inflammatory and Antioxidant Agents

A library of 3,5-diaryl-1-carbothioamide-pyrazoline (5a–j), N1-phenyl sulfonyl pyrazoline (6a–e) and pyrimidine (7a) analogs of combretastatin-A4 were synthesized and evaluated for their in vitro anticancer, anti-inflammatory and antioxidant activity. Results of in vitro assay against human breast cancer cell line (MCF-7) showed several compounds endowed with significant cytotoxicity compared to the adriamycin, a standard anticancer drug. Among the compounds synthesized, 7a was found to possess significant antiproliferative activity (GI50 < 0.1 µM) against the MCF-7 cell line as good as adriamycin (GI50 < 0.1 µM) whereas, compounds 6c, 5j and 5g also displayed good cytotoxicity (GI50 = 25.3–42.6 µM). Besides this, most active compound 7a was also evaluated against human myeloid leukemia cell line K562 and the remarkable result was obtained with GI50 < 0.1 µM, comparable to that of adriamycin (GI50 < 0.1 µM). In addition, all the synthesized compounds were evaluated for their anti-inflammatory and antioxidant activity. The percent inhibition studies revealed that most of the compounds were found to possess substantial anti-inflammatory and antioxidant activities. This work is licensed under a Creative Commons Attribution 4.0 International License