INSIGHTS INTO THIORIDAZINE FOR ITS ANTI-TUBERCULAR ACTIVITY FROM MOLECULAR DOCKING STUDIES

摘要

Objective: Thioridazine (TZ) is a drug that has been used for over 35 years as a psychoactive drug, is now potentially utilized in combination with certain anti-TB drugs to cure MDR, XDR and TDR TB. The current study explores the plausible reasons for its anti-tubercular activity through molecular docking procedure. Methods: Molecular docking were performed by using the molecular modeling software Glide ? from the suite of Schr?dinger Inc., Molecular docking studies were performed to study the binding affinity of Thioridazine on the active sites of various Mycobacterium tuberculosis enzymes in an effort to increase the understanding of the action of Thioridazine (TZ) as an antitubercular agent. Seventeen enzymes from different mechanisms were docked and the resulting glide scores (G-Scores) were tabulated. Results: The enzyme CmaA2 - Cyclopropane mycolic acid synthase (PDB id: 1KPI) scored lowest binding energy which means the greater stability of the thioridazine’s ability to bind to the receptor. MmaA2 (1TPY), InhA (2NSD) and PknG (2PZI) enzymes of Mycobacterium tuberculosis gave the best G-scores. Conclusion: The docking study results revealed that Thioridazine may act by more than one possible mechanism to exert anti-tubercular activity against MDR (Multi Drug Resistant), XDR (Extensively Drug Resistant) and TDR (Totally Drug Resistant) -TB. Keywords: Thioridazine (TZ), Efflux pumps, Molecular docking, Enzymes, Binding energy, MDR, XDR.