Synthesis, characterization, and pharmacological evaluation of novel azolo- and azinothiazinones containing 2,4-dihydroxyphenyl substituent as anticancer agents.

Abstract

We reported the synthesis and characterization of a series of azolo- and azino[1,3]thiazinones containing the 2,4-dihydroxyphenyl substituent. The compounds were prepared by a new one-step reaction of aryl-modified sulfinylbis[(2,4-dihydroxyphenyl)methanethione]s and the corresponding aminoazolo(azino)carboxamides. Their chemical structures were confirmed by IR, NMR: 1H, 13C, HSQC, and EI-MS spectral data. The compounds inhibited proliferation and viability of lung cancer A549, colon cancer HT-29, and glioma C6 cells in a structure- and concentration-dependent manner. The activity of some analogues was below 10 μmol dm−3 (IC50). Glioma C6 cells were the most sensitive to tested compounds. Generally, the derivatives were not toxic for the skin fibroblast HSF culture. Moreover, some of them exerted a protective effect on the treated normal cells. Evaluation of compound properties in silico showed that they possess significant drug-like characteristics and most of them display a low toxicity.Graphical abstract