Anticancer activity of structural hybrids of various 5/6-memberedheterocycles with pyrazolobenzothiazine 5,5-dioxide

Abstract

Thiophene, furan, coumarin and pyrazolobenzothiazine are well familiar for their biological activities. In this research, pyrazolobenzothiazine ring system is hybridized with various S, N & O-containing heterocycles and the resulting compounds were screened for their anticancer activity against six different cancer cell lines i.e., KB (human oral carcinoma cells), MCF-7(human breast carcinoma cells), A549 (human alveolar adenocarcinoma cells), Hep-G2 (liver carcinoma cells), SGC-7901(human gastric carcinoma cells) and S1 (human colon carcinoma cells) using MTT assay. Most of the compounds exhibited good activity against KB, S1 and A549 cancer cell lines. 5k and 5p appeared as potent inhibitors of KB cell line with IC50 values 2.78 and 4.39 μM respectively, 5q was a potent inhibitor of MCF-7 (IC50 value = 13.64 μM) and 5j an excellent inhibitor of A549 cell line having IC50value of 1.03 μM. 5p and 5q were inhibitors of S1 cell line (IC50 values of 8.29 μM and 7.69 μM respectively), whereas, 5o and 5q as inhibitors of Hep-G2 cell line were discovered. A number of compounds show activity exceeding that of 5-fluoruracil in different cell assays. The most potently active compounds, 5j, 5p and 5q, exhibited selectivity in targeting cancerous cells as compared to normal human PBM cells while, 5k and 5o displayed significant toxicity in normal cells.