Synthesis, Molecular Docking, and Biological Evaluation of a New Series of Benzothiazinones and Their Benzothiazinyl Acetate Derivatives as Anticancer Agents against MCF-7 Human Breast Cancer Cells and as Anti-Inflammatory Agents.

Six 1,4-benzothiazin-3-ones ( 2a - f ) and four benzothiazinyl acetate derivatives ( 3a - d ) were synthesized and characterized by various spectroscopic methods, namely, 1 H NMR, 13 C NMR, IR, MS, and elemental analysis. The cytotoxic effects of the compounds were assessed against MCF-7, a human breast cancer cell line, along with their anti-inflammatory activity. Molecular docking studies performed against the VEGFR2 kinase receptor displayed a common binding orientation of the compounds in the catalytic binding pocket of the receptor. The generalized Born surface area (GBSA) studies of compound 2c with the highest docking score also proved its stability in binding to the kinase receptor. Compounds 2c and 2b showed better results against VEGFR2 kinase with IC 50 values of 0.0528 and 0.0593 μM, respectively, compared to sorafenib. All of the compounds ( 2a - f and 3a - d ) showed effective growth inhibition having (IC 50 ) values of 2.26, 1.37, 1.29, 2.30, 4.98, 3.7, 5.19, 4.50, 4.39, and 3.31 μM, respectively, against the MCF-7 cell line compared to standard 5-fluorouracil (IC 50 = 7.79 μM). However, compound 2c displayed remarkable cytotoxic activity (IC 50 = 1.29 μM), suggesting it as a lead compound in the cytotoxic assay. Additionally, compounds 2c and 2b showed better results against VEGFR2 kinase with IC50 values of 0.0528 and 0.0593 μM, respectively, compared to sorafenib. It also inhibited hemolysis by stabilizing the membrane comparable to that of diclofenac sodium, a standard used in the human red blood cell membrane stabilization assay and hence can act as a template for designing novel anticancer and anti-inflammatory agents.