Structural Insight into the Mechanism of 4-Aminoquinolines Selectivity for the alpha2A-Adrenoceptor.

ABSTRACT:

Background

α_2A-adrenoceptor (AR) is a potential target for the treatment of degenerative diseases of the central nervous system, and α_2A-AR agonists are effective drugs for this condition. However, the lack of high selectivity for α_2A-AR subtype of traditional drugs greatly limits their clinic usage.

Methods

A series of homobivalent 4-aminoquinolines conjugated by two 4-aminoquinoline moieties via varying alkane linker length (C2-C12) were characterized for their affinities for each α₂-AR subtype. Subsequently, docking, molecular dynamics and mutagenesis were applied to uncover the molecular mechanism.

Results

Most 4-aminoquinolines (4-aminoquinoline monomer, C2-C6, C8-C10) were selective for α_2A-AR over α_2B<

SUBMITTER: Li Z 

PROVIDER: S-EPMC7340475 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature