Design and synthesis of atorvastatin derivatives with enhanced water solubility, hepatoselectivity and stability.

ABSTRACT: Statins are effective 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-R) inhibitors, which are successfully used for cardiovascular disease treatment. Statins' side effects are generally attributed to poor bioavailability and hepatoselectivity, which are closely related to their high lipophilicity. Targeted delivery of statins to the liver is considered as a way to reduce unwanted side effects. Herein we report on synthesis and evaluation of atorvastatin conjugates targeting the galactose-specific hepatic asialoglycoprotein receptor (ASGPR). The prepared conjugates showed greater water solubility compared to unmodified atorvastatin. The synthesised compounds demonstrated potent binding to the ASGPR with submicromolar K _D values. The conjugates with an amide bond conn

SUBMITTER: Maklakova SY 

PROVIDER: S-EPMC9890652 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature