Xylatolides A and B, new 10-membered macrolides from the endophytic fungus Xylaria sp.

Chemical investigation of the fungal endophyte Xylaria sp. isolated from leaves of Moringa oleifera, collected in Cameroon, resulted in the previously undescribed 10-membered macrolide, and two known natural products. The structures of the xylatolides A and B were unambiguously identified by their mass spectra and by extensive 1D and 2D NMR spectroscopic analysis, featuring a 10-membered lactone core structure with oxygenated substituents and an unsubstituted 10-alkyl chain presenting seven carbon atoms. Compounds were screened for their cytotoxic potential against the human HepG2 hepatocellular carcinoma cells and HCT-116 cells (human colon carcinoma cell line). Moreover, the isolated compounds were also assayed against a small panel of sensitive strains including the bacterial species Escherichia coli, Staphylococcus aureus, and Mycobacterium tuberculosis as well as against the fungal species Candida albicans. However, no significant activities were found.

Bioactive constituents from Trichilia dregeana Sond. (Meliaceae).

The chemical investigation of the methanolic leaf extract of Trichilia dregeana Sond. led to the isolation of a hitherto unreported cycloartane-type triterpene, dregeanol (1), together with nine known compounds, (3ß,23E)-9,19-cyclolanosta-23,25-dien-3-ol (2), 9,19-cyclolanost-24-en-23-one (3), 6ß-hydroxystigmasta-4,22-dien-3-one (4), lyoniresinol (5), maslinic acid (6), asperphernamate (7), mixture of stigmasterol (8) and ß-sitosterol (9) and ß-sitosterol-3-O-ß-D-glucopyranoside (10). The structures of the isolates were elucidated by extensive spectroscopic and spectrometric analyses (1D and 2D NMR, ESI-MS) and by comparison with previously reported data. Compounds 2 and 6 showed significant antibacterial effect against Escherichia coli and Salmonella enteritidis, res-pectively, with MIC value of 31.25 µg/mL, whilst they displayed moderate antifungal effect with MIC value of 62.5 µg/mL against Candida albicans. All the isolates except compound 3 were found to possess a weak antioxidant potential in the DPPH, ABTS and FRAP assays.

Chemical constituents from Ficus sur Forssk (Moraceae).

Phytochemical investigation of the aerial roots of Ficus sur, a Cameroonian medicinal plant, resulted in a previously undescribed cerebroside, suroside (1), in addition to its aglycon congener suramide (2). Moreover, six known natural products including alpinumisoflavone (3), wighteone metabolite (4), oleanolic acid (5), ß-sitosterol (6), ß-sitosterol-3-O-ß-D-glucopyranoside (7), and epi-ѱ-taraxastanolone (8) were identified. The structures of the previously undescribed compounds were determined by analysis of 1D and 2D-NMR (One and two dimensional nuclear magnetic resonance), mass spectrometry, chemical conversion, and by comparison of these data with those from the literature. Wighteone metabolite (4) exhibited a weak cytotoxic activity against the human HepG2 hepatocellular carcinoma cells with an IC50 value of 51.9 µM.

Prenylated cyclohexene-type meroterpenoids and sulfur-containing xanthones produced by Pseudopestalotiopsis theae.

Chemical investigation of the fungal endophyte Pseudopestalotiopsis theae isolated from leaves of Caloncoba welwitschii, collected in Cameroon, resulted in two previously undescribed sulfur-containing xanthone derivatives sydoxanthones D and E, in addition to three previously undescribed monomeric diisoprenyl-cyclohexene-type meroterpenoids biscognienynes D-F and five known natural products. The structures of the undescribed compounds were unambiguously identified by their mass spectra and by extensive 1D and 2D NMR spectroscopic analysis. Mosher's reaction was performed to determine the absolute configuration of sydoxanthones D and E while TDDFT-ECD calculations were used to assign the configuration of biscognienyne D. Biscognienynes B and D showed significant cytotoxicity against the mouse lymphoma cell line L5178Y with IC50 values of 7.7 and 6.7 µM and against the human leukemic cell lines HL60, and Hal-01 with IC50 values ranging from 4.3 to 12.1 µM.

Natural Products Impacting DNA Methyltransferases and Histone Deacetylases.

Epigenetics refers to heritable changes in gene expression and chromatin structure without change in a DNA sequence. Several epigenetic modifications and respective regulators have been reported. These include DNA methylation, chromatin remodeling, histone post-translational modifications, and non-coding RNAs. Emerging evidence has revealed that epigenetic dysregulations are involved in a wide range of diseases including cancers. Therefore, the reversible nature of epigenetic modifications concerning activation or inhibition of enzymes involved could be promising targets and useful tools for the elucidation of cellular and biological phenomena. In this review, emphasis is laid on natural products that inhibit DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) making them promising candidates for the development of lead structures for anticancer-drugs targeting epigenetic modifications. However, most of the natural products targeting HDAC and/or DNMT lack isoform selectivity, which is important for determining their potential use as therapeutic agents. Nevertheless, the structures presented in this review offer the well-founded basis that screening and chemical modifications of natural products will in future provide not only leads to the identification of more specific inhibitors with fewer side effects, but also important features for the elucidation of HDAC and DNMT function with respect to cancer treatment.

Sesquiterpenoids from the Endophytic Fungus Rhinocladiella similis.

Ten new sesquiterpenoid derivatives, rhinomilisins A-J (1-10), along with six known analogues (11-16), were isolated from the mangrove-derived endophytic fungus Rhinocladiella similis. The structures of the new compounds were elucidated by their NMR and MS data, while the absolute configuration of 3 and 6 was determined by X-ray crystallographic analysis and Mosher's method, respectively. All isolated compounds (1-16) were evaluated for their cytotoxicity against the mouse lymphoma cell line L5178Y, and compounds 1, 7, and 15 showed moderate activity with IC50 values of 5.0, 8.7, and 24.4 µM, respectively.

Terpenoids from Turraeanthus species.

Chemical investigation of the root bark of Turraeanthus mannii and the stem of T. longipes resulted in the isolation of two new diterpenes, 13-methyl-labda-8(17)-en-15-oic acid (1) and 13-(hydroxymethyl)-14-hydroxy-ent-labda-8(17)-en-15-oic acid (2), along with two known diterpenes, 19-hydroxy-ent-labda-8(17),13-dien-15,16-olide (3) and 19-acetoxy-ent-labda-8(17),13-dien-15,16-olide (4), and the phytosterol, stigmasterol. The structure elucidation of the new compounds has been achieved using spectroscopic techniques.