Antimicrobial Potential of Betulinic Acid and Investigation of the Mechanism of Action against Nuclear and Metabolic Enzymes with Molecular Modeling

Abstract

Natural products have important pharmacological activities. This study sought to investigate the activity of the compound betulinic acid (BA) against different strains of bacteria and fungi. The minimum inhibitory concentration (MIC) was determined and then the minimum bactericidal concentration (MBC) and minimum fungicidal concentration (MFC). After performing the in vitro tests, molecular modeling studies were carried out to investigate the mechanism of action of BA against the selected microorganisms. The results showed that BA inhibited the growth of microbial species. Among the 12 species (Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa, Escherichia coli, Mycobacterium tuberculosis, Candida albicans, C. tropicalis, C. glabrata, Aspergillus flavus, Penicillium citrinum, Trichophyton rubrum, and Microsporum canis) investigated, 9 (75%) inhibited growth at a concentration of 561 µM and 1 at a concentration of 100 µM. In general, the MBC and MFC of the products were between 561 and 1122 μM. In silico studies showed that BA presented a mechanism of action against DNA gyrase and beta-lactamase targets for most of the bacteria investigated, while for fungi the mechanism of action was against sterol 14α-demethylase (CYP51) targets and dihydrofolate reductase (DHFR). We suggest that BA has antimicrobial activity against several species.

In vitro antibacterial activity of betulinic acid from Psidium guajava L

“…The in vitro antibacterial effect of betulinic acid on some selected clinical bacterial strains shows that betulinic has significant antibacterial effects against the tested organisms. Previous studies have reported the antimicrobial and anticancer activity of betulinic acid from other plants (Lou, et al, 2021;Rodrigues, et al, 2023) [13,14] . This is an initial report of the antibacterial effects of betulinic acid from the leaves of Psidium guajava L.…”

Protective Role of Betulinic Acid against Cisplatin-Induced Nephrotoxicity and Its Antibacterial Potential toward Uropathogenic Bacteria

“…The MICs of betulinic acid were detected using broth microdilution technique using Muller-Hinton broth (Oxoid, UK) in microtitration plates. The lowest concentration of betulinic acid, which caused an inhibition of bacterial growth, was documented as MIC value [ 35 ].…”

Tuning of the Anti-Breast Cancer Activity of Betulinic Acid via Its Conversion to Ionic Liquids

“…Betulinic acid (BA) is a lupane-type pentacyclic triterpene that is found in the bark of several plants and is industrially isolated from plants of Betula species [ 12 ]. It has shown great pharmacological potential due to its wide variety of biological activities, including anti-tumor, anti-inflammatory, anti-oxidative, anti-diabetic, anti-malarial, antibacterial, antiviral, antifungal, and some other properties [ 12 , 13 , 14 , 15 ]. Among these, the anti-tumor properties of BA have been studied the most extensively.…”