Design of novel tazarotene derivatives as potential antipsoriatic drugs: physicochemical properties study and molecular docking analysis of their binding to retinoic acid receptor family (RAR-alpha, RAR-beta and RAR-gamma)

Design of novel antipsoriatic drugs based on the medicinal compound Tazarotene is the main purpose of the present study. Firstly, the molecular structures of Tazarotene and its derivatives (F, Cl, CH۳, OCH۳, COOH, OH, NH۲ and CF۳) were optimized using density functional theory (DFT) at B۳LYP/۶-۳۱۱++G (d, p) computational method. Then, the optimized molecules were docked into the active site of the retinoic acid receptors. The molecular docking analyses revealed that, the Tazarotene derivatives with COOH, CF۳ and OCH۳ substituents can make strongest complexes with RAR-alpha, RAR-beta and RAR-gamma, respectively. Based on the physicochemical properties calculations, it was cleared that the CF۳ derivative of Tazarotene has better properties (receptor-ligand interaction efficiency, lipophilicity and skin permeation) compared with that of the Tazarotene.

Keywords:

Antipsoriatic drugs , Drug design , Molecular docking , Molecular Simulation , retinoic acid receptor , Tazarotene