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

• Published in: Monatshefte für Chemie 2015, Vol.146 (8), p.1315-1327
• Main Authors: Matysiak, Joanna, Juszczak, Małgorzata, Karpińska, Monika M., Langner, Ewa, Walczak, Katarzyna, Lemieszek, Marta, Skrzypek, Alicja, Rzeski, Wojciech, Niewiadomy, Andrzej
• Format: Article
• Language: English
• Subjects: Analytical Chemistry; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Inorganic Chemistry; Organic Chemistry; Original Paper; Physical Chemistry; Theoretical and Computational Chemistry
• ISSN: 0026-9247; 1434-4475
• DOI: 10.1007/s00706-015-1453-4

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 10 μmol dm −3 (IC 50 ). 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