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)

Abstract

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, CH₃, OCH₃, COOH, OH, NH₂ and CF₃) were optimized using density functional theory (DFT) at B3LYP/6-311++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, CF₃ and OCH₃ 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 CF₃ derivative of Tazarotene has better properties (receptor-ligand interaction efficiency, lipophilicity and skin permeation) compared with that of the Tazarotene.