22 research outputs found
Marine bacterial inhibitors from the sponge-derived fungus Aspergillus sp
Chromatographic separation of a crude extract obtained from the fungus Aspergillus sp., isolated from the Mediterranean sponge Tethya aurantium, yielded a new tryptophan derived alkaloid, 34(1-hydroxy-3-(2methylbut-3-en-2-y1)-2-oxoindolin-3-yl)methyl)-1-methyl-3,4-dihydrobenzo[e][1,41diazepine-2, 5-dione (1), and a new meroterpenoid, austalide R (2), together with three known compounds (3-5). The structures of the new compounds were unambiguously elucidated on the basis of extensive one and twodimensional NMR (1H, 13C, COSY, HMBC, and ROESY) and mass spectral analysis. Interestingly, the compounds exhibited antibacterial activity when tested against a panel of marine bacteria, with 1 selectively inhibiting Vibrio species and 2 showing a broad spectrum of activity. In contrast, no significant activity was observed against terrestrial bacterial strains and the murine cancer cell line L5178Y. (C) 2014 Elsevier Ltd. All rights reserved.Chemistry, OrganicSCI(E)[email protected]
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
Two trypanocidal dipeptides from the roots of Zapoteca portoricensis (Fabaceae)
Zapoteca portoricensis (Jacq) HM Hernández is used with remarkable efficacy in ethnomedicinal management of tonsillitis in the Eastern part of Nigeria. Previous pharmacological studies have validated the antiinflammatory and antimicrobial activities of the crude extract. In this study, two dipeptides, saropeptate (aurantiamide acetate) and anabellamide, were isolated from the methanol root extract of Zapoteca portoricensis and their chemical structures deduced by one dimensional and two dimensional NMR and mass spectrometry. These compounds were isolated for the first time from this plant, and no report has been found on their previous isolation from the genus Zapoteca. Evaluation of their trypanocidal activity showed that compound 1 exhibited potent activity against Trypanosoma brucei rhodesiense with an IC50 value of 3.63 μM and selectivity index of 25.3
NF kappa B inhibitors and antitrypanosomal metabolites from endophytic fungus Penicillium sp. isolated from Limonium tubiflorum
Chemical investigation of the endophytic fungus Penicillium sp. isolated from Limonium tubiflorum growing in Egypt afforded four new compounds of polyketide origin, including two macrolides, penilactone (1) and 10,11-epoxycurvularin (2), a dianthrone, neobulgarone G (7), and a sulfinylcoumarin, sulfimarin (14), along with twelve known metabolites (3-6, 8-13, 15 and 16). The structures of all compounds were assigned by comprehensive spectral analysis (1D and 2D NMR) and mass spectrometry. Compounds 3, 4, 13 and 16 showed pronounced antitrypanosomal activity with mean MIC values ranging from 4.96 to 9.75μM. Moreover, when tested against a panel of three human tumor cell lines compounds 3, 4, 6 and 12 showed selective growth inhibition against Jurkat and U937 cell lines with IC(50) values ranging from 1.8 to 13.3μM. The latter compounds also inhibited TNFα-induced NF-κB activity in K562 cells with IC(50) values ranging from 1.6 to 10.1μM, respectively