Quantum chemical and molecular docking studies of some phenothiazine derivatives

Abstract

Phenothiazines are synthetic antipsychotics with a wide range of biological effects. Their properties are determined by the structure and variety of substituents in the heterocyclic system. It is known that various quantum chemical properties have a significant influence on drug behavior in biological systems. Because of the diversity in the chemical structure of phenothiazines and other drugs that include heterocyclic systems, quantum chemical calculations provide useful methods for predicting their effects. This study made an attempt to describe the physicochemical properties and the molecular docking simulation of phenothiazine derivatives. To predict the reactivity of phenothiazine derivatives, DFT-based descriptors including certain highest occupied molecular orbital and lowest unoccupied molecular orbital, energy gap, electronic chemical potential, chemical hardness, nucleophilicity, and electrophilicity were performed by using B3LYP / 6311 ++ G (d, p) level. The most and least active compounds were docked to the protein proteins glycosylphosphatidylinositol phospholipase D inhibitor (1GYM), anaphylatoxin receptor antagonist (6C1Q), arylacetonitrilase inhibitor (3UGC) and aspulvinone dimethylallyl transferase inhibitor (3RIX) to confirm the observations of DFT models and elucidate the mode of binding between this type of compound and the corresponding protein.