Synthesis of 2-(2,4-dihydroxyphenyl)thieno-1,3-thiazin-4-ones, their lipophilicity and anticancer activity in vitro.
A new one-step synthesis of novel biologically active 2-substituted 2,4-dihydroxyphenyl-4[Formula: see text]-thieno[3,2-[Formula: see text]][1,3]thiazin-4-ones and 4[Formula: see text]-thieno[2,3-[Formula: see text]][1,3]thiazin-4-ones has been elaborated and described. The compounds were prepared by the reaction of aryl-modified sulfinylbis [(2,4-dihydroxyphenyl)methanethione]s and the corresponding aminothiophenecarboxamides. The derivatives showed anticancer activity in vitro. These compounds inhibited the proliferation and viability of lung cancer A549, colon cancer HT-29 and glioma C6 cells in a concentration-dependent manner. Some of the derivatives had no influence on normal skin fibroblasts culture viability. Moreover, one compound (1b) showed the ability to inhibit DNA synthesis in cancer cells, especially in C6 cells, and was not toxic for normal oligodendrocytes and hepatocytes. Using reversed phase RP 18 HPLC and immobilised artificial membrane (IAM) chromatography the phase affinity of the compounds was determined. The influence of lipophilicity on the activity of compounds has been discussed.
Department of Chemistry, University of Life Sciences in Lublin, 20-950, Lublin, Poland. joanna.matysiak@up.lublin.pl.
Joanna
http://orcid.org/0000-0002-0363-4450
J
Matysiak
Department of Medical Biology, Institute of Rural Health in Lublin, Jaczewskiego 2, 20-090, Lublin, Poland.
Małgorzata
M
Juszczak
Institute of Industrial Organic Chemistry in Warsaw, Annopol 6, 03-236, Warsaw, Poland.
Monika M
MM
Karpińska
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.
Ewa
E
Langner
Department of Pharmacology, Medical University in Lublin, Chodźki 4a, 20-093, Lublin, Poland.
Katarzyna
K
Walczak
Department of Medical Biology, Institute of Rural Health in Lublin, Jaczewskiego 2, 20-090, Lublin, Poland.
Marta K
MK
Lemieszek
Department of Chemistry, University of Life Sciences in Lublin, 20-950, Lublin, Poland.
Alicja
A
Skrzypek
Department of Chemistry, University of Life Sciences in Lublin, 20-950, Lublin, Poland.|Institute of Industrial Organic Chemistry in Warsaw, Annopol 6, 03-236, Warsaw, Poland.
Andrzej
A
Niewiadomy
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.
Wojciech
W
Rzeski
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002845:Chromatography; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006801:Humans; D015394:Molecular Structure; D013843:Thiazines / Q000138:chemical synthesis* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D013843:Thiazines
Anticancer agents; Antiproliferative activity; Cytotoxicity; Lipophilicity; Resorcinols; Thieno-1,3-thiazin-4-ones