Antiprotozoal and Antibacterial Activity of Ravenelin, a Xanthone Isolated from the Endophytic Fungus Exserohilum rostratum

Abstract

The natural compound ravenelin was isolated from the biomass extracts of Exserohilum rostratum fungus, and its antimicrobial, antiplasmodial, and trypanocidal activities were evaluated. Ravenelin was isolated by column chromatography and HPLC and identified by NMR and MS. The susceptibility of Gram-positive and Gram-negative bacteria strains to ravenelin was determined by microbroth dilution assay. Cytotoxicity was evaluated in hepatocarcinoma cells (HepG2) and BALB/c peritoneal macrophages by using MTT. SYBR Green I-based assay was used in the asexual stages of Plasmodium falciparum. Trypanocidal activity was tested against the epimastigote and intracellular amastigote forms of Trypanosoma cruzi. Ravenelin was active against Gram-positive bacteria strains, with emphasis on Bacillus subtilis (MIC value of 7.5 µM). Ravenelin’s antiparasitic activities were assessed against both the epimastigote (IC50 value of 5 ± 1 µM) and the intracellular amastigote forms of T. cruzi (IC50 value of 9 ± 2 µM), as well as against P. falciparum (IC50 value of 3.4 ± 0.4 µM). Ravenelin showed low cytotoxic effects on both HepG2 (CC50 > 50 µM) and peritoneal macrophage (CC50 = 185 ± 1 µM) cells with attractive selectivity for the parasites (SI values > 15). These findings indicate that ravenelin is a natural compound with both antibacterial and antiparasitic activities, and considerable selectivity indexes. Therefore, ravenelin is an attractive candidate for hit-to-lead development.

Fungal Endophytes: A Potential Source of Antibacterial Compounds

“…Aspergillus sp. YXf3, an endophyte residing inside the leaves of Ginkgo biloba, yielded some novel p-terphenyls named prenylterphenyllin D (187), prenylterphenyllin E (188), and 2 -O-methylprenylterphenyllin (189), along with the known compounds prenylterphenyllin (190) and prenylterphenyllin B (191,Figure 11). Compounds 187-191 displayed antibacterial activity against X. oryzae pv.…”

“…Ravenelin (440, Figure 24) was extracted from Exserohilum rostratum, an endophyte of Phanera splendens, an endemic medicinal plant of the Amazon region. Ravenelin (440) displayed antibacterial activity against B. subtilis and S. aureus with MIC values of 7.5 and 484 µM, respectively (amoxicillin MIC against B. subtilis and S. aureus 1.3 and 21.4 µM; another positive control terramycin MIC against B. subtilis and S. aureus 16.3 and 16.3 µM, respectively) [190].…”

Bioprospecting the Antibacterial Activity of Endophytic Fungi from Noni (Morinda citrifolia) against Bacterial Spot of the Passion Fruit Tree

“…Some studies have shown that compounds isolated from endophytic fungi have antimicrobial activity against the phytopathogenic bacteria of the Xanthomonas genus [28,29]. Thus, the ACN extract was fractionated in CC, giving fractions FACN1 to FACN6; these fractions were analyzed by 1 H NMR, and fractions FACN4 and FACN5 showed spectrums with patterns of xanthones, which is a class of compound that has reported diverse biological activities [30][31][32]. Isolation by CC procedure led to the compounds S1 and S2.…”

Overview of Bioactive Fungal Secondary Metabolites: Cytotoxic and Antimicrobial Compounds

“…From the Brazilian biodiversity, the fungus Exserohilum rostratum ( Figure 6 ) was isolated from Bauhinia guianensis [ 209 ] and Phanera splendens [ 210 ], which are typical Amazonian plants used in popular medicine to combat infections. Among the SMs produced by this species are the polyketide monocerin, ergosterol peroxide, annularins, and ravenelin, which presented moderated antimicrobial activity on B. subtilis , S. aureus , E. coli , P. aeruginosa , and B. subtilis and Salmonella typhimurium [ 209 , 210 ].…”