title: Synthesis and Anticancer Activity of 2-(Alkyl-, Alkaryl-, Aryl-, Hetaryl-)-[1,2,4]triazolo[1,5-c]quinazolines.
abstract: 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 (1)H, (13)C 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.
authors.affiliation: Organic and Bioorganic Chemistry Department, Zaporizhzhya State Medical University, Mayakovsky Ave. 26, 69035, Zaporizhzhya, Ukraine.
authors.forename: Sergiy I
authors.initials: SI
authors.lastname: Kovalenko
authors.forename: Lyudmyla M
authors.initials: LM
authors.lastname: Antypenko
authors.forename: Andriy K
authors.initials: AK
authors.lastname: Bilyi
authors.forename: Sergiy V
authors.initials: SV
authors.lastname: Kholodnyak
authors.forename: Olexandr V
authors.initials: OV
authors.lastname: Karpenko
authors.forename: Olexii M
authors.initials: OM
authors.lastname: Antypenko
authors.forename: Natalya S
authors.initials: NS
authors.lastname: Mykhaylova
authors.forename: Tetyana I
authors.initials: TI
authors.lastname: Los
authors.forename: Olexandra S
authors.initials: OS
authors.lastname: Kolomoets
keywords: 2-Alkyl (alkaryl-, aryl-, hetaryl-)[1,2,4]triazolo[1,5-c]quinazolines; Anticancer activity; Carboxylic acid (3H-quinazoline-4-ylidene)hydrazides; N-(R-Benzylidene)-N′-(3H-quinazoline-4-ylidene)hydrazines; [1,2,4]Triazolo[1,5-c]quinazolines