Synthesis of 5-arylidene-2-amino-4-azolones and evaluation of their anticancer activity.
Series of novel 5-arylidene-2-arylaminothiazol-4(5H)-ones and 2-aryl(benzyl)amino-1H-imidazol-4(5H)-ones were synthesized from appropriate 2-alkylthioazol-4-ones using nucleophilic substitution in position 2 by various anilines and benzylamines and Knoevenagel reaction. X-ray structural studies of 22 revealed the structure to be intermediate between amino and imino tautomeric forms. All the target compounds were evaluated for the anticancer activity in vitro in standard National Cancer Institute 60 cancer cell lines assay. Majority of compounds showed significant antitumor cytotoxicity effect at micromolar and submicromolar level (Mean LogGI50 ranges -5.77 to -4.35). Some of the most potent compounds, namely 10 and 13, possessed selectively high effect on all leukemia cell lines at submicromolar level (Mean LogGI50 [leukemia lines], respectively, -6.41 and -6.29), which are probably associated with immunosuppressive activity. Individual cancer cell lines sensitivity to synthesized compounds and SAR studies are discussed. COMPARE analysis allowed to disclose probable modes of anticancer action for synthesized compounds, in particular showed number of high correlations with activity patterns of alkylating agents (PCC approximately 0.606-0.731).
Subtel'na
Ivanna
I
Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, Ukraine.
Atamanyuk
Dmytro
D
Szymańska
Ewa
E
Kieć-Kononowicz
Katarzyna
K
Zimenkovsky
Borys
B
Vasylenko
Olexandr
O
Gzella
Andrzej
A
Lesyk
Roman
R
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007093:Imidazoles