Molecular Insights into the Interaction of Ursolic Acid and Cucurbitacin from Colocynth with Therapeutic Targets of Mycobacterium tuberculosis

Abstract

Aims: Medicinal plants like Citrullus colocynthis are a potential choice to produce helpful novel antimycobacterial drugs. The existence of a range of natural products in the plants, especially Ursolic Acid (UA) and cucurbitacin E 2-0-β-d-glucopyranoside (CEG), with promising antibacterial activity against a variety of bacteria, prompted the need to check its actions against Mycobacterium tuberculosis (Mtb). Background: Mycobacterium tuberculosis (Mtb), an obligate human pathogen causes tuberculosis and is one of the major causes of death worldwide. A few combinations of drugs are currently accessible for treating TB patients, but these are inadequate to tackle worldwide TB cases. Objective: The molecular interactions between ursolic acid and cucurbitacin E with the eight potential Mtb target proteins were investigated with the objective of finding drug-like inhibitors. Methods: Avogadro v.1.2.0 and Openbabel v.2.4.1 were used for creating file formats required for docking analysis. Molecular docking was performed with eight different proteins essential for Mtb metabolism and survival. AutoDock v.4.2 and AutoDock vina v.1.1.2 were used for docking and Gromacs 5.1.4 was used for simulation studies. Results and Discussion: Among the two ligands used in this research, cucurbitacin E showed a better docking score relative to the drugs presently available for all the target proteins. Rifampicin showed the best binding affinity (among known inhibitors) i.e. -10.8 kcal/mol with C terminal caspase recruitment domain. Moreover, ursolic acid and cucurbitacin E showed uniform binding score (above -7.5 kcal/mol) with all the target proteins, acknowledged its availability as a potential multi-target drug. Conclusion: Ursolic acid can be useful in the creation of novel, multi-targeted and effective anti- TB medicines since it showed stable structure with FabH.