Design, synthesis and antibacterial activity of novel 7-thiazolo[3,2-]-1,2,4-triazin-7-one derivatives.

Based on the observed biological activity of 1,2,4-triazin-5-one derivatives and their cyclic analogues, a novel series of 7-thiazolo[3,2-]-1,2,4-triazin-7-one derivatives that contain ester moiety compounds carboxylic acid moiety compounds and piperazine amide moiety compounds at position-3 of the thiazolotriazinone scaffold were synthesized. The intermolecular cyclization occurred regioselectively at N2-position of 1,2,4-triazine ring was characterized by X-ray single-crystal diffraction analysis. The biological activities of the target compounds were assayed against some bacterial strains. Compared with ciprofloxacin, compounds and exhibited more excellent antibacterial activity, especially the activity against , showing that the fluorine at the para position of the benzyl group would be the best choice. In addition, compounds with carboxylic acid moiety can enhance the antibacterial activity. Compounds containing bulky 1-(substituted phenyl)piperazine moiety were found with slightly less biological activity. Similar to ciprofloxacin, the docking result of target compounds with DNA topoisomerase II indicates the carboxyl group of the target compounds with carboxylic acid moiety has a crucial salt bridge interaction with Mg in the protein.