The combinatorial library of novel potential anticancer agents, namely, 2-(аlkyl-, alkaryl-, aryl-, hetaryl-)[1,2,4]triazolo[1,5-
c]quinazolines, was synthesized by the heterocyclization of the аlkyl-, alkaryl-, aryl-, hetarylcarboxylic acid (3
Н-quinazoline-4-ylidene)hydrazides by oxidative heterocyclization of the 4-(arylidenehydrazino)quinazolines using bromine, and by the heterocyclization of
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The combinatorial library of novel potential anticancer agents, namely, 2-(аlkyl-, alkaryl-, aryl-, hetaryl-)[1,2,4]triazolo[1,5-
c]quinazolines, was synthesized by the heterocyclization of the аlkyl-, alkaryl-, aryl-, hetarylcarboxylic acid (3
Н-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 (3
H-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(3
H)-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.
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