Alkaloids from the mangrove-derived actinomycete Jishengella endophytica 161111.
A new alkaloid, 2-(furan-2-yl)-6-(2S,3S,4-trihydroxybutyl)pyrazine (1), along with 12 known compounds, 2-(furan-2-yl)-5-(2S,3S,4-trihydroxybutyl)pyrazine (2), (S)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (3), (S)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (4), (4S)-4-(2-methylbutyl)-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (5), (S)-4-benzyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (6), flazin (7), perlolyrine (8), 1-hydroxy-β-carboline (9), lumichrome (10), 1H-indole-3-carboxaldehyde (11), 2-hydroxy-1-(1H-indol-3-yl)ethanone (12), and 5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde (13), were isolated and identified from the fermentation broth of an endophytic actinomycetes, Jishengella endophytica 161111. The new structure 1 and the absolute configurations of 2-6 were determined by spectroscopic methods, J-based configuration analysis (JBCA) method, lactone sector rule, and electronic circular dichroism (ECD) calculations. Compounds 8-11 were active against the influenza A virus subtype H1N1 with IC50 and selectivity index (SI) values of 38.3(±1.2)/25.0(±3.6)/39.7(±5.6)/45.9(±2.1) μg/mL and 3.0/16.1/3.1/11.4, respectively. The IC50 and SI values of positive control, ribavirin, were 23.1(±1.7) μg/mL and 32.2, respectively. The results showed that compound 9 could be a promising new hit for anti-H1N1 drugs. The absolute configurations of 2-5, 13C nuclear magnetic resonance (NMR) data and the specific rotations of 3-6 were also reported here for the first time.
Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. wangpei850212@163.com.
Pei
P
Wang
Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. kongfandong501@126.com.
Fandong
F
Kong
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China. rxwzq@163.com.
Jingjing
J
Wei
Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. wangyi0213@ouc.edu.cn.
Yi
Y
Wang
Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. wwwakin@ouc.edu.cn.
Wei
W
Wang
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China. rxwzq@163.com.
Kui
K
Hong
Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. weimingzhu@ouc.edu.cn.
Weiming
W
Zhu
D039903:Actinobacteria / Q000737:chemistry*; D000470:Alkaloids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004396:Coloring Agents; D005285:Fermentation; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D018517:Plant Roots / Q000382:microbiology; D043982:Rhizophoraceae / Q000382:microbiology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013778:Tetrazolium Salts; D013844:Thiazoles
D000470:Alkaloids; D000998:Antiviral Agents; D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue