In Silico evaluation of the potential of phytochemicals from Cissus populnea against Mycobacterium tuberculosis

Abstract

The study investigated the anti-tubercular potential of the phytochemicals of the extracts of Cissus populnea (C. populnea) via in silico methods. Some phytochemicals from the plant were screened against Mycobacterium tuberculosis type II dehydroquinase (MTBII DHQase) and Pantothenate Synthetase (PS) using molecular docking techniques. Against MTBII DHQase, luteolin and catechin had the highest docking scores among the compounds from C. populnea, even higher than that of clofazimine, the reference drug. Against PS, the results also revealed that luteolin and poncirin had the highest scores among the compounds, also higher than that of pyrazinamide, a standard PS inhibitor. The compounds interacted with key amino acid residues in the proteins’ binding pockets. Molecular dynamic simulation of the lead compounds revealed stability of the complexes at the binding pocket of the proteins, with the average root mean-squared deviation all below 2.5 Å. The best models generated from quantitative structure-activity relationships were kpls_desc_6 and kpls_desc_47, with standard deviation values of 0.405 and 0.7829, respectively, indicating closeness between the predicted and observed values, while the R² values were 0.7283 and 0.9156, respectively, underscoring the models’ ability in making predictions. The model kpls_desc_6 predicted a pIC₅₀ of 5.008 μM for catechin against MTBII DHQase, while the model kpls_desc_47 predicted pIC₅₀s of 5.407 μM and 5.362 μM for luteolin and poncirin, respectively, against PS. The fitness score generated by e-pharmacophore modeling showed that all compounds except cis-octadecanoic acid, methyl ester, scored above the standard drugs. Further clinical and preclinical investigations should be conducted on the phytochemicals from C. populnea in a bid to harness their full potential as anti-TB agents.