The combinatorial library of novel potential anticancer agents, namely, 2-(alkyl -, alkaryl-, aryl-, hetaryl-) [1,2,4]triazolo [1,5-c]quinazolines, was synthesized by the heterocyclization of the alkyl -, alkaryl-, aryl-, hetarylcarboxylic acid (3H-quinazoline-4-ylidene)hydrazides by oxidative heterocyclization of the 4-(arylidenehydrazino)quinazolines using bromine, and by the heterocyclization of N-(2-cyanophenyl)formimidic acid ethyl ester. The optimal method for synthesis of the s-triazolo [1,5-c]quinazolines appeared to be cyclocondensation of the corresponding carboxylic acid (3H-quinazoline-4-ylidene)hydrazides. The compounds' structures were established by 1H, 13C NMR, LC-and EI-MS analysis. The in vitro screening of anticancer activity determined the most active compound to be 3,4,5-trimethoxy-N'-[quinazolin-4(3H)-ylidene]benzohydrazide (3.20) in micromolar concentrations with the GI50 level (MG_MID, GI50 is 2.29). Thus, the cancer cell lines whose growth is greatly inhibited by compound 3.20 are: non-small cell lung cancer (NCI-H522, GI50=0.34), CNS (SF-295, GI50=0.95), ovarian (OVCAR-3, GI50=0.33), prostate (PC-3, GI50=0.56), and breast cancer (MCF7, GI50=0.52), leukemia (K-562, GI50=0.41; SR, GI50=0.29), and melanoma (MDA-MB-435, GI50=0.31; SK-MEL-5, GI50=0.74; UACC-62, GI50=0.32). SAR-analysis is also discussed. © Kovalenko et al.; licensee Österreichische Apotheker-Verlagsgesellschaft m. b. H., Vienna, Austria.
Kovalenko, S. I., Antypenko, L. M., Bilyi, A. K., Kholodnyak, S. V., Karpenko, O. V., Antypenko, O. M., … Kolomoyets, O. S. (2013). Synthesis and anticancer activity of 2-(alkyl-, alkaryl-, aryl-, hetaryl-) [1,2,4]triazolo [1,5-c]quinazolines. Scientia Pharmaceutica, 81(2), 359–391. https://doi.org/10.3797/scipharm.1211-08