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Design, synthesis, and negative inotropic evaluation of 4‐phenyl‐1 H ‐1,2,4‐triazol‐5(4 H )‐one derivatives containing triazole or piperazine moieties
Author(s) -
Wei ZhiYu,
Cui BaiRi,
Cui Xun,
Wu YanLing,
Fu Yang,
Liu LiPing,
Piao HuRi
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12828
Subject(s) - contractility , chemistry , piperazine , nifedipine , inotrope , glibenclamide , pharmacology , hela , triazole , medicine , cell , biochemistry , calcium , endocrinology , organic chemistry , diabetes mellitus
In this study, four novel series of 4‐phenyl‐1 H ‐1,2,4‐triazol‐5(4 H )‐one derivatives containing triazole or piperazine moieties were designed, synthesized, and evaluated for negative inotropic activity by measuring the left atrium stroke volume in isolated rabbit heart preparations. Almost all of the compounds showed an ability to moderate the cardiac workload by decreasing the heart rate and contractility. Among them, 7h was found to be the most potent with a change in stroke volume of −48.22 ± 0.36% at a concentration of 3 × 10 −5 mol/L (metoprolol: −9.74 ± 0.14%). The cytotoxicity of these compounds was evaluated using the human cervical cancer cell line HeLa, the liver cancer cell line Hep3B, and the human normal hepatic cell line LO 2. A preliminary study of the mechanism of action for the compound 7h on the regulation of atrial dynamics with ATP ‐sensitive K + channel and L‐type Ca 2+ channel blockers glibenclamide and nifedipine was performed in the isolated perfused beating rabbit atria.