title: Exploring the chemodiversity and biological activities of the secondary metabolites from the marine fungus Neosartorya pseudofischeri.
abstract: The production of fungal metabolites can be remarkably influenced by various cultivation parameters. To explore the biosynthetic potentials of the marine fungus, Neosartorya pseudofischeri, which was isolated from the inner tissue of starfish Acanthaster planci, glycerol-peptone-yeast extract (GlyPY) and glucose-peptone-yeast extract (GluPY) media were used to culture this fungus. When cultured in GlyPY medium, this fungus produced two novel diketopiperazines, neosartins A and B (1 and 2), together with six biogenetically-related known diketopiperazines,1,2,3,4-tetrahydro-2, 3-dimethyl-1,4-dioxopyrazino[1,2-a]indole (3), 1,2,3,4-tetrahydro-2-methyl-3-methylen e-1,4-dioxopyrazino[1,2-a]indole (4), 1,2,3,4-tetrahydro-2-methyl-1,3,4-trioxopyrazino[1,2-a] indole (5), 6-acetylbis(methylthio)gliotoxin (10), bisdethiobis(methylthio)gliotoxin (11), didehydrobisdethiobis(methylthio)gliotoxin (12) and N-methyl-1H-indole-2-carboxamide (6). However, a novel tetracyclic-fused alkaloid, neosartin C (14), a meroterpenoid, pyripyropene A (15), gliotoxin (7) and five known gliotoxin analogues, acetylgliotoxin (8), reduced gliotoxin (9), 6-acetylbis(methylthio)gliotoxin (10), bisdethiobis(methylthio) gliotoxin (11) and bis-N-norgliovictin (13), were obtained when grown in glucose-containing medium (GluPY medium). This is the first report of compounds 3, 4, 6, 9, 10 and 12 as naturally occurring. Their structures were determined mainly by MS, 1D and 2D NMR data. The possible biosynthetic pathways of gliotoxin-related analogues and neosartin C were proposed. The antibacterial activity of compounds 2-14 and the cytotoxic activity of compounds 4, 5 and 7-13 were evaluated. Their structure-activity relationships are also preliminarily discussed.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. natprodlwl@gmail.com.
authors.forename: Wan-Ling
authors.initials: WL
authors.lastname: Liang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. lexiu2012@163.com.
authors.forename: Xiu
authors.initials: X
authors.lastname: Le
authors.affiliation: School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China. ceslhj@mail.sysu.edu.cn.
authors.forename: Hou-Jin
authors.initials: HJ
authors.lastname: Li
authors.affiliation: Guangdong Institute of Gastroenterology, Guangzhou 510655, China. morningyang100@gmail.com.
authors.forename: Xiang-Ling
authors.initials: XL
authors.lastname: Yang
authors.affiliation: Guangdong Institute of Gastroenterology, Guangzhou 510655, China. junxiong_ch@sina.com.
authors.forename: Jun-Xiong
authors.initials: JX
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. junxu@biochemomes.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Guangdong Institute of Gastroenterology, Guangzhou 510655, China. huanliang.liu@gmail.com.
authors.forename: Huan-Liang
authors.initials: HL
authors.lastname: Liu
authors.affiliation: Institute of Chinese Medical Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China. wanglaiyou@gdpu.edu.cn.
authors.forename: Lai-You
authors.initials: LY
authors.lastname: Wang
authors.affiliation: Institute of Chinese Medical Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China. kuntengwang@gmail.com.
authors.forename: Kun-Teng
authors.initials: KT
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. kunchao89@gmail.com.
authors.forename: Kun-Chao
authors.initials: KC
authors.lastname: Hu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. lssydp@mail.sysu.edu.cn.
authors.forename: De-Po
authors.initials: DP
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. lanwj@mail.sysu.edu.cn.
authors.forename: Wen-Jian
authors.initials: WJ
authors.lastname: Lan
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D054659:Diketopiperazines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D005912:Gliotoxin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D055326:Neosartorya / Q000302:isolation & purification / Q000378:metabolism*; D064210:Secondary Metabolism; D013215:Starfish / Q000382:microbiology*; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D054659:Diketopiperazines; D005912:Gliotoxin