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
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.
Conclusions: Ursolic acid can be useful in the creation of novel, multi-targeted and effective anti-
TB medicines since it showed stable structure with FabH.