Decalactone Derivatives from Corynespora cassiicola, an Endophytic Fungus of the Mangrove Plant Laguncularia racemosa

被引:40
作者
Ebrahim, Weaam [2 ,3 ]
Aly, Amal H. [2 ]
Mandi, Attila [1 ]
Totzke, Frank [4 ]
Kubbutat, Michael H. G. [4 ]
Wray, Victor [5 ]
Lin, Wen-Han [6 ]
Dai, Haofu [7 ]
Proksch, Peter [2 ]
Kurtan, Tibor [1 ]
Debbab, Abdessamad [2 ]
机构
[1] Univ Debrecen, Dept Organ Chem, H-4010 Debrecen, Hungary
[2] Univ Dusseldorf, Inst Pharmazeut Biol & Biotechnol, D-40225 Dusseldorf, Germany
[3] Mansoura Univ, Fac Pharm, Dept Pharmacognosy, Mansoura 35516, Egypt
[4] ProQinase GmbH, D-79106 Freiburg, Germany
[5] Helmholtz Ctr Infect Res, D-38124 Braunschweig, Germany
[6] Peking Univ, Natl Res Labs Nat & Biomimet Drugs, Hlth Sci Ctr, Beijing 100083, Peoples R China
[7] Chinese Acad Trop Agr Sci, Inst Trop Biosci & Biotechnol, Haikou 571101, Hainan, Peoples R China
关键词
Natural products; Medicinal chemistry; Drug discovery; Fungi; Structure elucidation; Conformation analysis; Lactones; CYTOTOXIC METABOLITES; BIOACTIVE METABOLITES; SALT-STRESS; DEHYDROCURVULARIN; CONSTITUENTS; HEPTAKETIDES; POLYKETIDES; INHIBITORS; CURVULARIN; TOLERANCE;
D O I
10.1002/ejoc.201200245
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Chemical investigation of the ethyl acetate extract of Corynespora cassiicola, isolated from leaf tissues of the Chinese mangrove medicinal plant Laguncularia racemosa, yielded four new secondary metabolites, including three decalactones, xestodecalactones DF (13) as well as corynesidone C (4), in addition to four known compounds. The structures of the new compounds were determined on the basis of one- and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry. Absolute configurations of the optically active compounds 13 were determined by TDDFT ECD calculations of their solution conformers, proving that they belong to the (11S) series of xestodecalactones, opposite to the (11R) configuration of the known xestodecalactones AC. All compounds were tested against a panel of human protein kinases. Among the isolated compounds, two inhibited several kinases such as IGF1-R and VEGF-R2 with IC50 values mostly in the low micromolar range.
引用
收藏
页码:3476 / 3484
页数:9
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