Structural requirements of the ASBT by 3D-QSAR analysis using aminopyridine conjugates of chenodeoxycholic acid.

ABSTRACT: The human apical sodium-dependent bile acid transporter (ASBT) is a validated drug target and can be employed to increase oral bioavailability of various drug conjugates. The aim of the present study was to investigate the chemical space around the 24-position of bile acids that influences both inhibition and uptake by the transporter. A series of 27 aminopyridine and aminophenol conjugates of glutamyl-chenodeoxycholate were synthesized and their ASBT inhibition and transport kinetics (parametrized as K(i), K(t), and J(max)) measured using stably transfected ASBT-MDCK cells. All conjugates were potent ASBT inhibitors. Monoanionic conjugates exhibited higher inhibition potency than neutral conjugates. However, neutral conjugates and chloro-substituted monoanionic conjugates were not substra

SUBMITTER: Zheng X 

PROVIDER: S-EPMC5745029 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature