Bioactive secondary metabolites from Trichoderma viride MM21: structure elucidation, molecular docking and biological activity.

Four bioactive metabolites; ergosterol (1), peroxy ergosterol (2), α-cyclopiazonic acid (3) and kojic acid (4), were isolated from the fungal sp. Trichoderma viride MM21. Their structures were assigned by cumulative analysis of NMR and mass spectra, and comparison with literature. The antimicrobial activity of the fungus supernatant, mycelial cake, cumulative crude extract and compounds 1-4 was broadly studied against 11 diverse pathogens, revealing auspicious activity results. Based on the molecular docking, ergosterol (1) and peroxy ergosterol (2) were picked up to be computationally tested against topoisomerase IV of Staphylococcus aureus. The nominated enzyme is a possible target for the antibacterial activity of triterpenoidal/steroidal compounds. Compounds 1, 2 showed a deep inserting inside the enzyme groove recording a good binding affinity of -8.1 and -8.4 kcal/mol, respectively. Noteworthy that the antibacterial activity of ergosterol was higher (14-17 mm) than peroxy ergosterol (11-14 mm), although ergosterol formed only one hydrogen bond with the target, while peroxy ergosterol formed three hydrogen bonds. Such higher antibacterial activity of ergosterol may be attributed to its interference with other proteins included in this inhibition. The cytotoxic activity was tested against brine shrimp, revealing 100% mortality for the supernatant, crude extract and whole isolated compounds. Such strong cytotoxicity is attributed most likely to the abundant productivity/concentration of α-cyclopiazonic acid and kojic acid.

A new diketopiperazine alkaloid from Aspergillus oryzae.

Investigation of bioactive secondary metabolites from terrestrial Aspergillus oryzae sp. MMAO1 using M2 medium afforded a new diketopiperazine alkaloid, 7,9-dihydroxy-3-(1H-indol-3-ylmethyl)-8-methoxy-2,3,11,11a-tetrahydro-6H-pyrazino[1,2-b]isoquinoline-1,4-dione (1a), containing the unusual amino acid L-6,8-dihydroxy-7-methoxyphenylalanine. This was co-isolated with ditryptophenaline (2), cyclo-(Tryp,Tyr) (4), cyclo-(Pro,Val), α-cyclopiazonic acid (3), kojic acid and uridine. Re-cultivation of the fungal strain on Dox medium led to the production of bisdethio(bismethylthio)gliotoxin (5), pseurotin A (6) along with linoleic acid, α-cyclopiazonic acid (3) and kojic acid. The chemical structure of the new diketopiperazine alkaloid including the relative configuration was determined by 1D and 2D NMR spectroscopy and HR-ESI-MS spectrometry, and by comparison with the related literature. The new alkaloid (1a) showed no antimicrobial activity or cytotoxicity against brine shrimps.

Chromophenazines from the terrestrial Streptomyces sp. Ank 315.

The new chromophenazines A-F [9-methyl-5-(3'-methylbut-2'-enyl)-5H-benzo[a]phenazin-7-one (1a), 9-methyl-5-(3'-methylbut-2'-enyl)-7-oxo-5,7-dihydrobenzo[a]phenazine-1-carboxylic acid (1b), 5-(3'-methylbut-2'-enyl)-7-oxo-5,7-dihydrophenazine-1-carboxamide (2), 3-benzoyl-5-(3'-methylbut-2'-enyl)-5,10-dihydrophenazine-1-carboxylic acid (5a), 3,7-dibenzoyl-5-(3'-methylbut-2'-enyl)-5,10-dihydrophenazine-1-carboxylic acid (5b), and 3,7-dibenzoyl-5-(3'-methylbut-2'-enyl)-5,10-dihydrophenazine-1-carboxamide (5c)], together with phenazine-1-carboxylic acid, 1-phenazinecarboxamide, 1-phenazinol, tryptophol, and anthranilic acid, were isolated from Streptomyces sp. Ank 315. The structures of the new compounds were established on the basis of spectroscopic data, 1D NOE, 2D NMR, and ESIMS measurements and comparison with literature values.