The continuous emergence of multidrug-resistant (MDR) bacteria drastically reduced the efficacy of our antibiotic armory and consequently, increased the frequency of therapeutic failure. The search for bioactive constituents from endophytic fungi against MDR bacteria became a necessity for alternative and promising strategies, and for the development of novel therapeutic solutions. We report here the isolation and structure elucidation of antibacterial and cytotoxic compounds from Phomopsis sp., an endophytic fungus associated with Garcinia kola nuts. The fungus Phomopsis sp. was isolated from the nut of Garcinia kola. The crude extract was prepared from mycelium of Phomopsis sp. by maceration in ethyl acetate and sequentially fractionated by column chromatography. The structures of isolated compounds were elucidated on the basis of spectral studies and comparison with published data. The isolated compounds were evaluated for their antibacterial and anticancer properties by broth microdilution and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide methods respectively. The samples were also tested spectrophotometrically for their hemolytic properties against human red blood cells. The fractionation of the crude extract afforded three known cytochalasins including 18-metoxycytochalasin J (1), cytochalasins H (2) and J (3) together with alternariol (4). The cytochalasin compounds showed different degrees of antibacterial activities against the tested bacterial pathogens. Shigella flexneri was the most sensitive microorganism while Vibrio cholerae SG24 and Vibrio cholerae PC2 were the most resistant. Ampicillin did not show any antibacterial activity against Vibrio cholerae NB2, Vibrio cholerae PC2 and Shigella flexneri at concentrations up to 512 μg/mL, but interestingly, these multi-drug resistant bacterial strains were sensitive to the cytochalasin metabolites. These compounds also showed significant cytotoxic properties against human cancer cells (LC50 = 3.66–35.69 μg/mL) with low toxicity to normal non-cancer cells. The three cytochalasin compounds isolated from the Phomopsis sp. crude extract could be a clinically useful alternative for the treatment of cervical cancer and severe infections caused by MDR Shigella and Vibrio cholerae.

Twenty-two compounds were isolated from the fruit of Albizia lebbeck including one unprecedented, rare amino acid-derived zwitterionic and one new flavone derivative. The isolation was performed on repeated column chromatography over silica gel and their structures were determined by 1D-, 2D-NMR and HR-ESI-MS spectra together with reported data in the literature. The chemophenetic significance is also discussed. Some isolated compounds were reported for the first time to be found in the species. Additionally, compound 2 showed antibacterial activity and compounds 1 and 2 revealed moderate cytotoxic activity against the Raw 264.7 cancer cell line with IC₅₀ values of 37.19 µM and 29.36 µM, respectively. Furthermore, a proposed biosynthetic pathway of compound 1 is described.

Three previously undescribed natural products, phomopsinin A – C (1 – 3), together with three known compounds, namely, cis-hydroxymellein (4), phomoxanthone A (5) and cytochalasin L-696,474 (6), were isolated from the solid culture of Phomopsis sp. CAM212, an endophytic fungus obtained from Garcinia xanthochymus. Their structures were determined on the basis of spectroscopic data, including IR, NMR, and MS. The absolute configurations of 1 and 2 were assigned by comparing their experimental and calculated ECD spectra. Acetylation of compound 1 yielded 1a, a new natural product derivative that was tested together with other isolated compounds on lipopolysaccharide-stimulated RAW 264.7 cells. Cytochalasin L-696,474 (6) was found to significantly inhibit nitric oxide production, but was highly cytotoxic to the treated cells, whereas compound 1 slightly inhibited nitric oxide production, which was not significantly different compared to lipopolysaccharide-treated cells. Remarkably, the acetylated derivative of 1, compound 1a, significantly inhibited nitric oxide production with an IC₅₀ value of 14.8 µM and no cytotoxic effect on treated cells, thereby showing the importance of the acetyl group in the anti-inflammatory activity of 1a. The study of the mechanism of action revealed that 1a decreases the expression of inducible nitric oxide synthase, cyclooxygenase 2, and proinflammatory cytokine IL-6 without an effect on IL-1β expression. Moreover, it was found that 1a exerts its anti-inflammatory activity in lipopolysaccharide-stimulated RAW 264.7 macrophage cells by downregulating the activation of ERK1/2 and by preventing the translocation of nuclear factor κB. Thus, derivatives of phomopsinin A (1), such as compound 1a, could provide new anti-inflammatory leads. Received: 29 November 2019 Accepted after revision: 02 July 2020 Publication Date: 05 August 2020 (online) Georg Thieme Verlag KG Stuttgart · New York

Objective. The present study investigated the effect of the leaves extracts and fractions of Plectranthus glandulosus on the inhibition of pancreatic lipase, cholesterol esterase, adipocytes lipid uptake, and antithrombotic activity which may be important in atherosclerosis development. Methods. Aqueous, ethanolic, and hydroethanolic extracts of Plactranthus glandulosus were prepared by maceration. The hydroethanolic extract was fractionated into n‐hexane, ethylacetate, and n-butanol fractions and their inhibition of pancreatic lipase, cholesterol esterase, adipocytes lipid uptake, and antithrombotic activities measured. Liquid chromatography‐high resolution mass spectrometry (LC‐HRMS) analysis was carried out to determine phytochemical constituents present in the extracts. Results. The standard orlistat exhibited a higher inhibitory activity on pancreatic lipase and cholesterol esterase (16.31 μg/mL and 15.75 μg/mL, respectively) compared to ethyl acetate fraction (IC₅₀, 17.70 μg/mL and IC₅₀, 24.8 μg/mL, respectively). Among crude extract, hydroethanolic extract showed a better inhibition against pancreatic lipase (IC₅₀, 21.06 μg/mL) and cholesterol esterase (IC₅₀, 25.14 μg/mL) though not comparable to the effect of orlistat. The best lipid uptake inhibition was observed in the hydroethanolic extract (IC₅₀, 45.42 μg/mL) followed by the ethyl acetate fraction (IC₅₀, 47.77 μg/mL). A better antithrombolytic activity was exhibited by the ethyl acetate fraction at all concentrations (50‐800 μ/mL), while hydroethanolic extract exhibited the best activity among crude extract. However, these were not comparable to the standard aspirin. The LC‐HRMS analysis revealed the presence of 7‐O‐methyl luteolin 5‐O‐β‐D‐glucopyranoside, chrysoeriol 5‐O‐β‐D‐glucopyranoside, 5,7‐dihydroxy‐3,2 ^′,4 ^′‐trimethoxyflavone, and plectranmicin as major compounds in both hydroethanolic extract and ethyl acetate fraction. Conclusion. Thus, our finding supports the traditional use of this plant, which might provide a potential source for future antiatherosclerotic drug discovery.

A new α-pyrone, asperpyrone (1) and two known compounds, stigmasterol (2) and 7-hydroxy-3-(2,3-dihydroxybutyl)-1(3H)-Isobenzofuranone (3) were isolated from the solid rice culture of the endophytic fungus Aspergillus sp., an endophytic fungus isolated from the fresh inner tissue of the barks of Garicinia smeathmannii. Their structures were determined by extensive spectral analysis including 1 D and 2 D NMR, HRESIMS and single-crystal X-ray crystallographic analysis. Asperpyrone (1) was tested against an axenic culture of Entamoeba moshkovskii, but did not exhibit any significant amoebicidal activity. Graphical abstract