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

Joanna Matysiak, Ma_gorzata Juszczak, MonikaM Karpi_ska, Ewa Langner, Katarzyna Walczak, Marta Lemieszek, Alicja Skrzypek, Wojciech Rzeski, Andrzej Niewiadomy

Index: Monatsh. Chem 146 , 1315-1327, (2015)

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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: (1)H, (13)C, 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 10moldm(-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.