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

Abstract

A library of 3,5-diaryl-1-carbothioamide-pyrazoline (5a-j), N 1-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.

Synthesis, characterization, molecular docking and in vitro anticancer activity of 3-(4-methoxyphenyl)-5-substituted phenyl-2-pyrazoline-1- carbothioamide

“…Globally, cancer is one of the serious and dreadful diseases characterized by the uncontrolled, rapid, and pathological proliferation of cells (Chavan et al, 2018). In underdeveloped countries incidence and mortality rate due to cancer increases day to day because of the growth and aging of the population (Suma et al, 2019).…”