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Synthesis, biological evaluation, and pharmacokinetic study of novel liguzinediol prodrugs.

ABSTRACT: Liguzinediol (LZDO) ester prodrugs 3-5 were synthesized and evaluated in vitro and in vivo for their potential use in prolonging the half-life of the parent drug LZDO (1a) in vivo. Prodrugs 3-5 were found to display a potent positive inotropic effect on the myocardium, without the risk of arrhythmia. Prodrugs 3-5 rapidly underwent enzymatic hydrolysis to release the parent compound LZDO in 1-3 h in rat liver microsomes and rat plasma. The half-life of the parent compound was prolonged after intragastric administration of prodrug 3, which was found to be a superior prodrug candidate for increasing myocardial contractility.

SUBMITTER: Liu Z

PROVIDER: S-EPMC6270099 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Synthesis, biological evaluation, and pharmacokinetic study of novel liguzinediol prodrugs.

Liu Zheng Z Li Wei W Wen Hong-Mei HM Bian Hui-Min HM Zhang Jing J Chen Lei L Chen Long L Yang Kun-Di KD

Molecules (Basel, Switzerland) 20130418 4

Liguzinediol (LZDO) ester prodrugs 3-5 were synthesized and evaluated in vitro and in vivo for their potential use in prolonging the half-life of the parent drug LZDO (1a) in vivo. Prodrugs 3-5 were found to display a potent positive inotropic effect on the myocardium, without the risk of arrhythmia. Prodrugs 3-5 rapidly underwent enzymatic hydrolysis to release the parent compound LZDO in 1-3 h in rat liver microsomes and rat plasma. The half-life of the parent compound was prolonged after intr ...[more]

PMID: 23599014

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