Secondary Metabolites with Nitric Oxide Inhibition from Marine-Derived Fungus Alternaria sp. 5102

Two new benzofurans, alternabenzofurans A and B (1 and 2) and two new sesquiterpenoids, alternaterpenoids A and B (3 and 4), along with 18 known polyketides (5−22), were isolated from the marine-derived fungus Alternaria sp. 5102. Their structures were elucidated on the basis of extensive spectroscopic analyses (1D and 2D NMR, HR-ESIMS, and ECD) and X-ray crystallography, as well as the modified Mosher’s method. Compounds 2, 3, 5, 7, 9–18, and 20–22 exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by lipopolysaccharide with IC50 values in the range from 1.3 to 41.1 μM. Structure-activity relationships of the secondary metabolites were discussed.

[1]  Lan Liu,et al.  A Review of Terpenes from Marine-Derived Fungi: 2015–2019 , 2020, Marine drugs.

[2]  A. Mándi,et al.  Alternarin A, a Drimane Meroterpenoid, Suppresses Neuronal Excitability from the Coral-Associated Fungi Alternaria sp. ZH-15. , 2020, Organic letters.

[3]  Jing Li,et al.  The Biological and Chemical Diversity of Tetramic Acid Compounds from Marine-Derived Microorganisms , 2020, Marine drugs.

[4]  R. Prasad,et al.  Endolichenic fungi: A hidden source of bioactive metabolites , 2020, South African Journal of Botany.

[5]  Shan He,et al.  A Review of Anti-Inflammatory Compounds from Marine Fungi, 2000–2018 , 2019, Marine drugs.

[6]  X. Liang,et al.  Novel anthraquinone derivatives as inhibitors of protein tyrosine phosphatases and indoleamine 2,3-dioxygenase 1 from the deep-sea derived fungusAlternaria tenuissimaDFFSCS013 , 2019, Organic Chemistry Frontiers.

[7]  Jianguo He,et al.  Penicamide A, A Unique N,N′-Ketal Quinazolinone Alkaloid from Ascidian-Derived Fungus Penicillium sp. 4829 , 2019, Marine drugs.

[8]  H. Schwalbe,et al.  (±) Alternarlactones A and B, Two Antiparasitic Alternariol-like Dimers from the Fungus Alternaria alternata P1210 Isolated from the Halophyte Salicornia sp. , 2019, The Journal of organic chemistry.

[9]  Jing Li,et al.  Anti-Inflammatory Cembrane-Type Diterpenoids and Prostaglandins from Soft Coral Lobophytum sarcophytoides , 2019, Marine drugs.

[10]  Guanghui Wang,et al.  Cytotoxic Components from Hypericum elodeoides Targeting RXRα and Inducing HeLa Cell Apoptosis through Caspase-8 Activation and PARP Cleavage. , 2019, Journal of natural products.

[11]  Xiao-jing Lin,et al.  Anti-inflammatory Mono- and Dimeric Sorbicillinoids from the Marine-Derived Fungus Trichoderma reesei 4670. , 2019, Journal of Natural Products.

[12]  Weiguang Sun,et al.  Bioactive secondary metabolites from the marine-associated fungus Aspergillus terreus. , 2018, Bioorganic chemistry.

[13]  Bin Yang,et al.  Perylenequione Derivatives with Anticancer Activities Isolated from the Marine Sponge-Derived Fungus, Alternaria sp. SCSIO41014 , 2018, Marine drugs.

[14]  Yongjun Lu,et al.  Anti-inflammatory meroterpenoids from the mangrove endophytic fungus Talaromyces amestolkiae YX1. , 2018, Phytochemistry.

[15]  Siwen Niu,et al.  New anti-inflammatory guaianes from the Atlantic hydrotherm-derived fungus Graphostroma sp. MCCC 3A00421 , 2018, Scientific Reports.

[16]  Jie Yuan,et al.  Antiviral and anti-inflammatory meroterpenoids: stachybonoids A–F from the crinoid-derived fungus Stachybotrys chartarum 952 , 2017 .

[17]  Xiu-li Yin,et al.  Sesteralterin and Tricycloalterfurenes A-D: Terpenes with Rarely Occurring Frameworks from the Marine-Alga-Epiphytic Fungus Alternaria alternata k21-1. , 2017, Journal of natural products.

[18]  Yongjun Lu,et al.  Lasiodiplactone A, a novel lactone from the mangrove endophytic fungus Lasiodiplodia theobromae ZJ-HQ1. , 2017, Organic & biomolecular chemistry.

[19]  Hongxin Liu,et al.  Two New Metabolites from the Endophytic Fungus Alternaria sp. A744 Derived from Morinda officinalis , 2017, Molecules.

[20]  Yabin Yang,et al.  Phytotoxic, antibacterial, and antioxidant activities of mycotoxins and other metabolites from Trichoderma sp. , 2017, Natural Product Research.

[21]  Hui Ding,et al.  Inhibitors of BRD4 Protein from a Marine-Derived Fungus Alternaria sp. NH-F6 , 2017, Marine drugs.

[22]  Z. She,et al.  Altenusin derivatives from mangrove endophytic fungus Alternaria sp. SK6YW3L , 2016 .

[23]  Shuyao Wang,et al.  Purification, Chemical Characterization, and Bioactivity of an Extracellular Polysaccharide Produced by the Marine Sponge Endogenous Fungus Alternaria sp. SP-32 , 2016, Marine Biotechnology.

[24]  Jae-Hyuk Jang,et al.  Inhibitory effects of alternaramide on inflammatory mediator expression through TLR4-MyD88-mediated inhibition of NF-кB and MAPK pathway signaling in lipopolysaccharide-stimulated RAW264.7 and BV2 cells. , 2016, Chemico-biological interactions.

[25]  Wai Yee Chan,et al.  Marine natural products with anti-inflammatory activity , 2015, Applied Microbiology and Biotechnology.

[26]  M. Metzler,et al.  Conjugation of the mycotoxins alternariol and alternariol monomethyl ether in tobacco suspension cells. , 2015, Journal of agricultural and food chemistry.

[27]  D. Tantillo,et al.  Branching out from the bisabolyl cation. Unifying mechanistic pathways to barbatene, bazzanene, chamigrene, chamipinene, cumacrene, cuprenene, dunniene, isobazzanene, iso-γ-bisabolene, isochamigrene, laurene, microbiotene, sesquithujene, sesquisabinene, thujopsene, trichodiene, and widdradiene sesqu , 2014, Journal of the American Chemical Society.

[28]  Guo-dong Chen,et al.  Xinshengin, the first altenusin with tetracyclic skeleton core from Phialophora spp.☆ , 2013 .

[29]  Ligang Zhou,et al.  Metabolites from Alternaria Fungi and Their Bioactivities , 2013, Molecules.

[30]  I. Abe,et al.  Induced production of mycotoxins in an endophytic fungus from the medicinal plant Datura stramonium L. , 2012, Bioorganic & medicinal chemistry letters.

[31]  X. Yao,et al.  Heptaketides with antiviral activity from three endolichenic fungal strains Nigrospora sp., Alternaria sp. and Phialophora sp. , 2012, Fitoterapia.

[32]  M. Shaaban,et al.  Seven naphtho-γ-pyrones from the marine-derived fungus Alternaria alternata: structure elucidation and biological properties , 2012, Organic and medicinal chemistry letters.

[33]  Yong-cheng Lin,et al.  Bioactive hydroanthraquinones and anthraquinone dimers from a soft coral-derived Alternaria sp. fungus. , 2012, Journal of natural products.

[34]  Liangdong Guo,et al.  Polyketides with antimicrobial activity from the solid culture of an endolichenic fungus Ulocladium sp. , 2012, Fitoterapia.

[35]  Ki Hyun Kim,et al.  New Cytotoxic δ-Valerolactones from Cornus walteri , 2011 .

[36]  Yong-cheng Lin,et al.  Three Bianthraquinone Derivatives from the Mangrove Endophytic Fungus Alternaria sp. ZJ9-6B from the South China Sea , 2011, Marine drugs.

[37]  M. Brimble,et al.  Heteroatom-directed reverse Wacker oxidations. Synthesis of the reported structure of (-)-herbaric acid. , 2010, The Journal of organic chemistry.

[38]  G. Bernardinelli,et al.  The use of X-ray crystallography to determine absolute configuration. , 2008, Chirality.

[39]  Rob W. W. Hooft,et al.  Determination of absolute structure using Bayesian statistics on Bijvoet differences , 2008, Journal of applied crystallography.

[40]  M. Köck,et al.  Oxepinamides A-C and fumiquinazolines H--I: bioactive metabolites from a marine isolate of a fungus of the genus Acremonium. , 2000, Chemistry.

[41]  D. Faulkner Marine natural products. , 2000, Natural product reports.

[42]  T. Kusumi,et al.  High-field FT NMR application of Mosher's method. The absolute configurations of marine terpenoids , 1991 .