| Abstrakt: |
The Combretum genus, with its few investigated members, has shown evidence-based justification for its extensive study in finding natural alternatives to various maladies. One of its species, Combretum platypetalum, has been traditionally used to treat diarrhea, pneumonia, dysmenorrhea, and infertility in women, with phytochemical investigations focusing on its leaves. The plant part(s) employed in the traditional practice are not explicitly mentioned in the literature, but several therapeutic properties have been confirmed. This study is a follow-up to previous metabolomic reports and a comprehensive biological investigation of the root extract, aimed at investigating the active compounds. The root was extracted by maceration, and compounds were isolated using various chromatographic techniques. Combrenorplatypta A, arjunolic acid, betulinic acid, and lupeol (2-4) were bioguidedly isolated from C. platypetalum root for the first time. The structures of the isolated compounds were established based on spectroscopic (1D NMR, 2D NMR, IR, UV, and ECD) and spectrometric (ESIMS) data as well as time-dependent density functional theory (TD-DFT) calculations. In vitro and computational antifungal activities of the compounds were investigated; after that, molecular docking analysis of structures (1-4) versus target (sterol 14α-demethylase) binding affinity for druggability was established. The MICs of in vitro bio-investigated compounds ranged from 2.30 µM to 15 µM, while computational antifungal investigations showed MICs from 4 nM to 49.86 nM. The compounds produced over six times the activity of fluconazole, a first-line antifungal drug. This study has identified the active sites and possible mechanisms of action of molecules against fungal pathogens. [ABSTRACT FROM AUTHOR] |
