ANTIBACTERIAL, ANTIDERMATOPHYTIC AND CYTOTOXIC SECONDARY METABOLITES FROM Bersama abyssinica subsp. abyssinica, subsp. paulliniodes AND THEIR ENDOPHYTIC FUNGI

Abstract

Infectious and non-infectious diseases have caused a huge burden to the affected people as well as the healthcare systems across the globe. Antimicrobial resistance is on the rise and becoming a major threat in the efforts to treat diseases. Medicinal plants and fungi offer alternative solutions to this challenge and Bersama abyssinica is one of the plants used for treatment of various diseases such as tumors, dysentery, and roundworm infestation. This study aimed to isolate secondary metabolites from the stem barks and leaves of two subsp. of B. abyssinica and their endophytic fungi. The stem bark and leaves of the two subsp. of B. abyssinica were collected from Mt. Elgon National Forest. A portion of the collected plant materials was used for fungal endophyte isolation while the other portion was dried for extraction of secondary metabolites. The isolated pure fungal endophytes were subjected to fermentation on solid media followed by subsequent extraction of secondary metabolites. The extracts from both plant material and endophytic fungi were subjected to fractionation using column chromatography over silica gel and Sephadex LH-20 followed by further purification by High-Performance Liquid Chromatography (HPLC). Structure elucidation of pure compounds was done using a combination of spectroscopic techniques that include 1D and 2D NMR spectroscopy and Liquid Chromatography Mass Spectrometry. The relative configurations were defined by single-crystal X-ray crystallography and Nuclear Overhauser Effect Spectroscopy (NOESY) correlations. Structures for thirty compounds (17 – 46) were successfully elucidated with eight previously undescribed compounds (17 – 19, 33 – 36, and 41). Paulliniogenin A (17), 16β- hydroxybersamagenin 1,3,5-orthoacetate (20), 1β-acetoxy-3β,5β-dihydroxy-15-methoxy-16,19- dioxobufa-14(15),20,22-trienolide (35), epicocconigrone A (44) showed cytotoxic activities against Hela (KB3.1) cell lines with IC50 in the range of 1.4 ± 0.77 μM and 5.9 ± 1.89 μM. 1,2,3,6- tetra-O-galloyl-β-D-glucose (24), epicoccolide B (43), epicocconigrone A (44) and eleganketal A (45) showed weak cytotoxicity ranging between 11.7 ± 6.78 μM and 35.82 ± 5.40 μM for mouse fibroblast (L929) cell lines. Compounds 24, 43, and 45 exhibited antibacterial activity against E. coli and B. subtilis with an MIC value of 33.3 μg/mL. Moreover, 45 exhibited antifungal activity against T. tonsurans with an MIC value of 18.75 μg/mL. The bioactive compounds are potential lead compounds for the development of new drugs.