title: 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.
authors.affiliation: Department of Chemistry, University of Life Sciences in Lublin, Akademicka 15, 20-950 Lublin, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Matysiak
authors.affiliation: Department of Medical Biology, Institute of Rural Health in Lublin, Jaczewskiego 2, 20-090 Lublin, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Juszczak
authors.affiliation: Institute of Industrial Organic Chemistry in Warsaw, Annopol 6, 03-236 Warsaw, Poland.
authors.forename: Monika M
authors.initials: MM
authors.lastname: Karpińska
authors.affiliation: Department of Medical Biology, Institute of Rural Health in Lublin, Jaczewskiego 2, 20-090 Lublin, Poland ; Department of Pharmacology, Medical University in Lublin, Chodźki 4a, 20-093 Lublin, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Langner
authors.affiliation: Department of Pharmacology, Medical University in Lublin, Chodźki 4a, 20-093 Lublin, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Walczak
authors.affiliation: Department of Medical Biology, Institute of Rural Health in Lublin, Jaczewskiego 2, 20-090 Lublin, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Lemieszek
authors.affiliation: Department of Chemistry, University of Life Sciences in Lublin, Akademicka 15, 20-950 Lublin, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Skrzypek
authors.affiliation: Department of Medical Biology, Institute of Rural Health in Lublin, Jaczewskiego 2, 20-090 Lublin, Poland ; Department of Virology and Immunology, Maria Curie-Skłodowska University in Lublin, Akademicka 19, 20-033 Lublin, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Rzeski
authors.affiliation: Department of Chemistry, University of Life Sciences in Lublin, Akademicka 15, 20-950 Lublin, Poland ; Institute of Industrial Organic Chemistry in Warsaw, Annopol 6, 03-236 Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Niewiadomy
keywords: ADMET; Antiproliferative activity; Azolothiazinones; Cytotoxicity; Resorcinols