Synthesis, Biological Evaluation, and Pharmacokinetic Study of Novel Liguzinediol Prodrugs

Molecules

Zheng Liu²  Wei Li¹  Hong-Mei Wen²  Hui-Min Bian²  Jing Zhang²  Lei Chen²  Long Chen² 

[1] id="af1-molecules-18-04561">School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210046, Jiangsu, Chi

关键词: liguzinediol;    liguzinediol prodrugs;    synthesis;    positive inotropic effect;    pharmacokinetics;   

DOI  :  10.3390/molecules18044561

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.