In silico study for prediction of novel bioactivities of the endophytic fungal alkaloid, mycoleptodiscin B for human targets.

Mycoleptodiscin B is a natural product extracted from the endophytic fungus Mycoleptodiscus sp. found in Sri Lanka and Panama with experimentally unexplored activities for human targets. In this study, a computational methodology was applied to determine druggable targets of mycoleptodiscin B. According to the computational toxicity and pharmacokinetics assessment, mycoleptodiscin B was proven to be a suitable drug candidate. Druggable targets for this compound, aromatase, acidic plasma glycoprotein and androgen receptor, were predicted using reverse docking. A two-step validation of those targets was performed using conventional molecular docking and molecular dynamic (MD) simulations, resulting in aromatase being determined as the potential therapeutic target. Based on molecular mechanics/Generalized Born Surface Area (GBSA) free energies and ligand stability inside the active site cavity during its 120 ns MD run, it can be concluded that mycoleptodiscin B is a potent aromatase inhibitor and could be subjected to further in vitro and in vivo experiments in the drug development pipeline. Consequently, natural product chemists can quickly identify the hidden medicinal properties of their miracle compounds using the computational approach applied in this research.

Antifeedant, contact toxicity and oviposition deterrent effects of phyllostine acetate and phyllostine isolated from the endophytic fungus Diaporthe miriciae against Plutella xylostella larvae.

BACKGROUND: Larvae of the diamond back moth (DBM), Plutella xylostella, are destructive cabbage pests causing economic losses worldwide. Continuous application of synthetic pesticides to control this pest has resulted in environmental pollution and resistant pest strains. Thus, there is a crucial need to seek natural alternatives with minimal detrimental effects. This study was designed to investigate the antifeedant activities of endophytic fungi of Cyperus iria and to determine the antifeedant, contact toxicity and oviposition deterrent activities of phyllostine acetate and phyllostine of the endophytic Diaporthe miriciae fungus. RESULTS: Two cyclohexeneoxidediones, phyllostine acetate (1) and phyllostine (2), isolated from an ethyl acetate extract of D. miriciae exhibited strong antifeedant, contact toxicity, and oviposition deterrent activities against P. xylostella. Phyllostine acetate (1) and phyllostine (2) showed feeding deterrent indexes of 100% at 50 µg cm-2 in the no-choice leaf disc assay and 50% feeding deterrence (DC50 ) values of 9 and 4.7 µg cm-2 respectively. The median lethal concentration (LC50 ) values of phyllostine acetate (1) and phyllostine (2) were 4.38 and 6.54 µg/larva in the contact toxicity assay. The oviposition deterrent indexes of the two compounds were 100% for phyllostine acetate (1) and 28.6% for phyllostine (2) at 50 µg cm-2 . CONCLUSION: Phyllostine acetate and phyllostine show promise as compounds for the control of P. xylostella. This study encourages further investigation of endophytic fungi of the family Cyperacea, for the development of natural pest control agents in agriculture. © 2019 Society of Chemical Industry.

Stable isotope feeding studies reveal a steroid 5(6→7)abeo ring contraction biogenesis for the antibiotic solanioic acid produced by cultures of the fungus Rhizoctonia solani.

Culture feeding experiments with [1-13C]-acetate, [2-13C]- acetate, and [1,2-13C]-acetate have shown that the steroid ring B contraction involved in the biogenesis of the unprecedented carbon skeleton of the antibiotic solanioic acid (1) by the fungus Rhizoctonia solani involves cleavage of the C-5/C-6 bond. The study revealed that 9-epi-solanioic acid (4), which spontaneously converts to solanioic acid (1), is also produced by the cultures and it may be the actual natural product.

Serpulanines A to C, N-Oxidized Tyrosine Derivatives Isolated from the Sri Lankan Fungus Serpula sp.: Structure Elucidation, Synthesis, and Histone Deacetylase Inhibition.

Serpulanines A (1), B (2), and C (3) have been isolated from extracts of the rare Sri Lankan macrofungus Serpula sp. The structures of 1, 2, and 3 were elucidated by a combination of spectroscopic and single-crystal X-ray diffraction analyses. Serpulanines A (1) and B (2) both contain the rare (E)-2-hydroxyimino hydroxamic acid functional group array. A proposed biogenesis for serpulanine B (2) suggests that its (E)-2-hydroxyimino hydroxamic acid moiety arises from a diketopiperazine precursor. Synthetic serpulanine A (1) inhibited class I/II histone deacetylases in murine metastatic lung carcinoma cells with an IC50 of 7 µM.

Antimicrobial activities of endophytic fungi of the Sri Lankan aquatic plant Nymphaea nouchali and chaetoglobosin A and C, produced by the endophytic fungus Chaetomium globosum.

Twenty distinct endophytic fungi were isolated from the surface-sterilized plant parts of Nymphaea nouchali and were identified using morphological and molecular techniques. At 300 µg/disc concentration, eight of the 20 fungal extracts exhibited antimicrobial activities against Staphylococcus aureus (ATCC 25923) and Bacillus cereus (ATCC 11778) while two within the eight showed activity against Pseudomonas aeruginosa (ATCC 9027) and Escherichia coli (ATCC 35218). Furthermore, investigation of the crude extract of Chaetomium globosum resulted in the isolation of two known cytochalasans, chaetoglobosin A and C, and their structures were elucidated and confirmed by mass and nuclear magnetic resonance (NMR) (1H, 13C, COSY, HSQC, HMBC and tROESY) spectral data. Chaetoglobosin A showed antibacterial activities against Bacillus subtilis (MIC 16 µg mL-1), Staphylococcus aureus (MIC 32 µg mL-1) and methicillin-resistant Staphylococcus aureus (MRSA, MIC 32 µg mL-1). This is the first study to report the isolation, identification and antimicrobial properties of endophytic fungi of N. nouchali in Sri Lanka.

Antimicrobial activities of endophytic fungi obtained from the arid zone invasive plant Opuntia dillenii and the isolation of equisetin, from endophytic Fusarium sp.

BACKGROUND: Opuntia dillenii is an invasive plant well established in the harsh South-Eastern arid zone of Sri Lanka. Evidence suggests it is likely that the endophytic fungal populations of O. dillenii assist the host in overcoming biotic and abiotic stress by producing biologically active metabolites. With this in mind there is potential to discover novel natural products with useful biological activities from this hitherto poorly investigated source. Consequently, an investigation of the antimicrobial activities of the endophytes of O. dillenii, that occupies a unique ecological niche, may well provide useful leads in the discovery of new pharmaceuticals. METHODS: Endophytic fungi were isolated from the surface sterilized cladodes and flowers of O. dillenii using several nutrient media and the antimicrobial activities were evaluated against three Gram-positive and two Gram-negative bacteria and Candida albicans. The two most bioactive fungi were identified by colony morphology and DNA sequencing. The secondary metabolite of the endophyte Fusarium sp. exhibiting the best activity was isolated via bioassay guided chromatography. The chemical structure was elucidated from the ESIMS and NMR spectroscopic data obtained for the active metabolite. The minimum inhibitory concentrations (MICs) of the active compound were determined. RESULTS: Eight endophytic fungi were isolated from O. dillenii and all except one showed antibacterial activities against at least one of the test bacteria. All extracts were inactive against C. albicans. The most bioactive fungus was identified as Fusarium sp. and the second most active as Aspergillus niger. The structure of the major antibacterial compound of the Fusarium sp. was shown to be the tetramic acid derivative, equisetin. The MIC's for equisetin were 8 µg mL(-1) against Bacillus subtilis, 16 µg mL(-1) against Staphylococcus aureus and Methicillin Resistant Staphylococcus aureus (MRSA). CONCLUSIONS: O. dillenii, harbors several endophytic fungi capable of producing antimicrobial substances with selective antibacterial properties. By producing biologically active secondary metabolites, such as equisetin isolated from the endophytic Fusarium sp., the endophytic fungal population may be assisting the host to successfully withstand stressful environmental conditions. Further investigations on the secondary metabolites produced by these endophytes may provide additional drug leads.

Solanioic Acid, an Antibacterial Degraded Steroid Produced in Culture by the Fungus Rhizoctonia solani Isolated from Tubers of the Medicinal Plant Cyperus rotundus.

Solanioic acid (1), a degraded and rearranged steroid that exhibits in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), has been isolated from laboratory cultures of the fungus Rhizoctonia solani obtained from tubers of the plant Cyperus rotundus collected in Sri Lanka. The structure of solanioic acid (1) was elucidated by detailed analysis of NMR data, a single crystal X-ray diffraction analysis of a reduction product 2, and Mosher ester analysis on a derivative of the natural product. Solanioic acid (1) has an unprecedented carbon skeleton.

Helvolic acid, an antibacterial nortriterpenoid from a fungal endophyte, Xylaria sp. of orchid Anoectochilus setaceus endemic to Sri Lanka.

An endophytic fungus was isolated from surface sterilized leaf segments of Anoectochilus setaceus, an orchid endemic to Sri Lanka, and was identified as Xylaria sp. by morphological characters and DNA sequencing. Bioassay-guided chromatographic fractionation of the organic extract of a laboratory culture of this fungus led to the isolation of the known antibacterial helvolic acid. Helvolic acid was active against the Gram-positive bacteria, Bacillus subtilis [minimal inhibitory concentrations (MIC), 2 µg mL-1] and methicillin-resistant Staphylococcus aureus (MIC, 4 µg mL-1).