Bioactive secondary metabolites from the endophytic fungus Chaetomium sp. isolated from Salvia officinalis growing in Morocco

This study reports the chemical investigation and cytotoxic activity of the secondary metabolites produced by the endophytic fungus Chaetomium sp. isolated from Salvia officinalis growing in Morocco. This plant was collected from the Beni-Mellal Mountain in Morocco and belongs to the Lamiaceae family and is named in Morocco “Salmia”. The endophytic fungus Chaetomium sp. was isolated from the tissues of the stem of this plant. The fungal strain was identified by PCR. The crude organic extract of the fungal strain was proven to be active when tested for cytotoxicity against L5178Y mouse lymphoma cells. Chemical investigation of the secondary metabolites showed that cochliodinol is the main component beside isocochliodinol. The structures of the isolated compounds were determined on the basis of NMR analysis (1H, 13C, COSY and HMBC) as well as by mass spectrometry using ESI (Electron Spray Ionisation) as source

New Natural Product from Botryosphaeria australis, an Endophyte from Mangrove Avicennia marina

Chemical investigation of the endophytic fungus Botryosphaeria australis isolated from Avicennia marina originally from Hainan Province, P.R. China, yielded a new compound botryosphaenin (1), from the class of napthoquinone, together with 5 known compounds, botryosterpene (2) and 5-hydroxy-2,7-dimethoxynaphthalene-1,4-dione (3) and its derivatives, 6-ethyl-5-hydroxy-2,7-dimethoxynaphthalene-1,4-dione (4), O-methylaspmenone (5), O-methylasparvenone (6) and 5-(carboxymethyl)-7-hydroxy-1,4a-dimethyl-6-methylene decahydron aphthalene-1-carboxylic acid (7). Their structures were determined on the basis of spectroscopic methods including 1D (1H, 13C, and DEPT) and 2D (COSY, HMQC, HMBC, and ROESY) NMR experiments and by mass spectroscopic measurements The new compounds, 1 showed activity against the bacterial pathogens Staphylococcus aureus, several Streptococcus species and Bacillus subtilis, but also against the eukaryotic cell lines THP-1 (human leukemia monocyte) and BALB/3T3 (mouse embryonic fibroblast)

Enniatin a Inhibits the Chaperone Hsp90 and Unleashes the Immune System Against Triple-Negative Breast Cancer

Low response rates and immune-related adverse events limit the remarkable impact of cancer immunotherapy. To improve clinical outcomes, preclinical studies have shown that combining immunotherapies with N-terminal Hsp90 inhibitors resulted in improved efficacy, even though induction of an extensive heat shock response (HSR) and less than optimal dosing of these inhibitors limited their clinical efficacy as monotherapies. We discovered that the natural product Enniatin A (EnnA) targets Hsp90 and destabilizes its client oncoproteins without inducing an HSR. EnnA triggers immunogenic cell death in triple-negative breast cancer (TNBC) syngeneic mouse models and exhibits superior antitumor activity compared to Hsp90 N-terminal inhibitors. EnnA reprograms the tumor microenvironment (TME) to promote CD8+ T cell-dependent antitumor immunity by reducing PD-L1 levels and activating the chemokine receptor CX3CR1 pathway. These findings provide strong evidence for transforming the immunosuppressive TME into a more tumor-hostile milieu by engaging Hsp90 with therapeutic agents involving novel mechanisms of action

Detection of Bioactive Exometabolites Produced by the Filamentous Marine Cyanobacterium Geitlerinema sp.

Marine cyanobacteria are noted for their ability to excrete metabolites with biotic properties. This paper focuses on such exometabolites obtained from the culture of the marine filamentous cyanobacterium Geitlerinema sp. strain, their purification and subsequent analyses. By this means the recoveries of the active compounds, a prerequisite for properly determining their concentration, are quantified here for the first time. We demonstrate a new procedure using Amberlite XAD-1180 resin in combination with the eluent isopropanol for extraction of the culture media and gas chromatography as simplified chemical analysis. This procedure reduced necessary bacteria cultivation time (from 150 to 21 days) at low volumes of culture media (300 mL) required for identification of two selected bioactive compounds: 4,4′-dihydroxybiphenyl and harmane