Guangwei Wu

Four New Chloro-Eremophilane Sesquiterpenes from an Antarctic Deep-Sea Derived Fungus, Penicillium sp. PR19N-1

A new chloro-trinoreremophilane sesquiterpene 1, three new chlorinated eremophilane sesquiterpenes 2–4, together with a known compound, eremofortine C (5), were isolated from an Antarctic deep-sea derived fungus, Penicillium sp. PR19N-1. Structures were established using IR, HRMS, 1D and 2D NMR techniques. In addition, the plausible metabolic network of these isolated products is proposed. Compound 1 showed moderate cytotoxic activity against HL-60 and A549 cancer cell lines.

Versixanthones A–F, Cytotoxic Xanthone–Chromanone Dimers from the Marine-Derived Fungus Aspergillus versicolor HDN1009

Six unusual xanthone-chromanone dimers, versixanthones A-F (1-6), featuring different formal linkages of tetrahydroxanthone and 2,2-disubstituted chroman-4-one monomers, were isolated from a culture of the mangrove-derived fungus Aspergillus versicolor HDN1009. The absolute configurations of 1-6, representing the central and axial chirality elements or preferred helicities, were established by a combination of X-ray diffraction analysis, chemical conversions, and TDDFT-ECD calculations. The interconversion of different biaryl linkages between 1 and 4 and between 2 and 3 in DMSO by a retro-oxa-Michael mechanism provided insight into the formation of the xanthone-chromanone dimers and supported the assignments of their absolute configurations. Compounds 1-6 exhibited cytotoxicities against the seven tested cancer cell lines, with the best IC50 value of 0.7 μM. Compound 5 showed further inhibitory activity against topoisomerase I.

Cladosins A-E, hybrid polyketides from a deep-sea-derived fungus, Cladosporium sphaerospermum.

Five new fungal hybrid polyketides, cladosins A-D (1-4), that contain a novel linear 6(3)-enamino-8,10-dihydroxy-tetraketide (1 and 2) or 6-enamino-7(8)-en-10-ol (3 and 4) moiety, as well as the biogenetically related cladosin E (5), were isolated from the deep-sea-derived fungus Cladosporium sphaerospermum 2005-01-E3. Their structures (1-5) were elucidated through a combination of spectroscopic data, chemical conversion, and both Moshers and Marfeys methods for stereochemical assignment. A plausible biogenetic pathway to 1-5 is proposed. Cladosin C (3) possesses mild anti-influenza A H1N1 virus activity.

Meroterpenoids with diverse ring systems from the sponge-associated fungus Alternaria sp. JJY-32.

Fifteen meroterpenoids (1-15) with diverse ring systems including an unprecedented oxaspiro[5.5]nonane-fused cyclohexenone (1), hydrogenated benzofurans (2-5), hydrogenated chromans (6, 7), hydrogenated cyclopenta[b]chromans (8-11), and four monocyclic structures (12-15) were isolated from the sponge-associated fungus Alternaria sp. JJY-32. The structures were elucidated by detailed spectroscopic analysis, including 2D NMR and electronic circular dichroism (ECD) calculations, and assisted by chemical derivatizations. On the basis of supplementation experiments with specific enzyme inhibitors and putative precursors, a shikimate-isoprenoid hybrid biosynthetic pathway is proposed. The NF-κB inhibitory activities of 1-15 were tested, and all of them, except 6 and 7 (IC50 > 100 μM), showed activities with IC50 values ranging from 39 to 85 μM in RAW264.7 cells.

Cladosins F and G, two new hybrid polyketides from the deep-sea-derived Cladosporium sphaerospermum 2005-01-E3

Two new fungal hybrid polyketides, cladosins F (1) and G (2), with rare 6(3)-enamino-8,10-dihydroxy-tetraketide system were discovered from the deep-sea-derived fungus Cladosporium sphaerospermum 2005-01-E3 guided by OSMAC approach. Their structures were elucidated on the basis of comprehensive spectroscopic analyses, and cytotoxicity, antitubercular, anti-influenza A H1N1 virus, and NF-κB inhibitory activities were evaluated.

Structure-based discovery of cytotoxic dimeric tetrahydroxanthones as potential topoisomerase I inhibitors from a marine-derived fungus

DNA topoisomerase I (Topo I) is an important anticancer drug target, and xanthone dimers are considered to be a new kind of Topo I inhibitor chemotypes. Based on the characteristics of dimeric xanthone structures, five new dimeric xanthones (1-5) and two known SAD isomers (6 and 7) were isolated from the mangrove-derived fungus Aspergillus vericolor. The absolute configurations of compounds 1-7, entailing both central and axial chirality elements, were established by a combination of ECD comparison, chemical conversions, and biogenetic considerations. Compounds 1-7 possessed high structural diversity and exhibited cytotoxicity at different levels. The selected new compounds 1, 2, and 5 showed Topo I inhibition properties and the most potent compound 1, an atropisomer of compound 2, was confirmed to inhibit Topo I-mediated DNA relaxation by targeting Topo I, thereby, arresting the cell cycle process and inducing necrosis in cancer cells. Molecular docking studies showed that compound 1 could bind DNA by π-π interaction and DNA Topo I by hydrogen bonds to form a ternary complex.

Cytotoxic Tetrahydroxanthone Dimers from the Mangrove-Associated Fungus Aspergillus versicolor HDN1009

Three new tetrahydroxanthone dimers, 5-epi-asperdichrome (1), versixanthones N (2), and O (3), were isolated from the mangrove-derived fungus Aspergillus versicolor HDN1009. Their structures, including the absolute configurations, were elucidated by NMR, HRMS, and circular dichroism (CD) experiments. Among them, compound 1 was the second example of tetrahydroxanthone dimers, which dimerized by a rare diaryl ether linkage and showed promising antibacterial activities against Vibrio parahemolyticus, Bacillus subtilis, Mycobacterium phlei, and Pseudomonas aeruginosa, with MIC values ranging from 100 μM to 200 μM; whilst compounds 2 and 3 exhibited extensive cytotoxicities against five cancer cell lines (HL-60, K562, H1975, MGC803, and HO-8910), with IC50 values ranging from 1.7 μM to 16.1 μM.

Aniline-Tetramic Acids from the Deep-Sea-Derived Fungus Cladosporium sphaerospermum L3P3 Cultured with the HDAC Inhibitor SAHA

Four new tetramic acids, cladosins H-K (1-4), and a related known compound, cladodionen (5), were isolated from the culture of the Mariana Trench (depth 6562 m) sediment-derived fungus Cladosporium sphaerospermum L3P3 treated with the histone deacetylase inhibitor SAHA (suberanilohydroxamic acid). Interestingly, compounds 1-5 existed as equilibrium E/ Z mixtures and 1-4 were the first cases of tetramic acids containing aniline moieties. Their structures including absolute configurations were elucidated through a combination of NMR, MS, and Moshers method, together with the consideration of biogenetic origins. Incubation experiments of exogenous aniline and N-phenyloctanamide revealed that the aniline moiety in cladosins H-K (1-4) is probably derived from the degradation of SAHA, indicating that the well-known histone deacetylase inhibitor SAHA could be metabolized by L3P3 and provide aniline as a precursor for biotransformation of chemically reactive polyketides. The cytotoxicity of 1-5 was evaluated against the PC-3, MGC-803, SH-SY5Y, HCT-116, K562, and HL-60 cell lines, and compound 2 showed promising cytotoxicity against the HL-60 cell line with an IC50 value of 2.8 μM.

CCDC 984115: Experimental Crystal Structure Determination

Related Article: Guangwei Wu, Guihong Yu, Tibor Kurtan, Attila Mandi, Jixing Peng, Xiaomei Mo, Ming Liu, Hui Li, Xinhua Sun, Jing Li, Tianjiao Zhu, Qianqun Gu, and Dehai Li|2015|J.Nat.Prod.|78|2691|doi:10.1021/acs.jnatprod.5b00636