Synthesis and biological activity of novel N-cycloalkyl-(cycloalkylaryl)-2-[(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-yl)thio]acetamides

In this paper the novel N-cycloalkyl-(cycloalkylaryl)-2-[(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-yl)thio]acetamides synthesis by aminolysis of activated by thionyl chloride or carbonyldiimidazole [(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)-thio]acetic acids and alkylation of the 3-R-6-thio-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones potassium salts with N-cycloalkyl-(cycloalkylaryl)-2-chloroacetamides are proposed. The structures of compounds are determined by 1H, 13C NMR, LC-MS and EI-MS analysis. The in vitro anticancer, antibacterial activity and Photobacterium leiognathi Sh1 bioluminescence inhibition of synthesized compounds were revealed. SAR results were discussed. Compound 4.10 was found to be the most anticancer active one, selectively influenced on the non-small cell lung and CNS cancer cell lines, especially on the HOP-92 (log GI50 = −6.01) and U251 (log GI50 = −6.00).

Graphical abstractThe novel synthesis methods of the N-cycloalkyl-(cycloalkylaryl)-2-[(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-yl)thio]acetamides are proposed. Anticancer and antibacterial activity, Photobacterium leiognathi Sh1 bioluminescence inhibition of synthesized compounds are discussed.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► The 6-thio-3-R-2H- [1,2,4]triazino[2,3-c]quinazoline-2-ones S-derivatives are obtained. ► Spectral data, anticancer and antibacterial activity are discussed. ► Cytotoxicity was measured with luminescent bacteria Photobacterium leiognathi. ► “Structure–activity” relationship is discussed.