Structure, Derivatization, and Antitumor Activity of New Griseusins from Nocardiopsis sp.

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• 作者：Jian He ; Ernst Roemer ; Corinna Lange ; Xueshi Huang ; Armin Maier ; Gerhard Kelter ; Yi Jiang ; Li-hua Xu ; Klaus-Dieter Menzel ; Susanne Grabley ; Heinz-Herbert Fiebig ; Cheng-Ling Jiang ; Isabel Sattler
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：October 18, 2007
• 年：2007
• 卷：50
• 期：21
• 页码：5168 - 5175
• 全文大小：186K
• 年卷期：v.50,no.21(October 18, 2007)
• ISSN：1520-4804

文摘

Four new griseusins, 4'-dehydro-deacetylgriseusin A (1) and 2a,8a-epoxy-epi-deacetylgriseusin B (2) asnew constitutional derivatives and epi-deacetylgriseusin A (3) and epi-deacetylgriseusin B (4) as newstereoisomers, were isolated from Nocardiopsis sp. (YIM80133, DSM16644). 4'-Dehydro-deacetylgriseusinA (1) showed pronounced cytotoxic potency (mean IC₅₀ = 0.430 M) combined with a significant selectivityfor mammary cancer, renal cancer, and melanoma in a panel consisting of 37 tumor cell lines. In a clonogenicassay with tumor cells from 51 solid tumors, 1 inhibited anchorage independent growth and in vitro colonyformation of tumor cells in a concentration-dependent and tumor type selective manner. As 1 was only aminor product, a semisynthetic preparation from the major metabolite, epi-deacetylgriseusin A (3), wasachieved. Our studies also yielded 9-hydroxy-epi-deacetylgriseusin B methylester (5), 4'-dehydro-9-hydroxy-deacetylgriseusin B methylester (6), and 4'-dehydro-2a,8a-epoxy-deacetylgriseusin B (7) as new syntheticisochromanequinone derivatives, which provided a basic structure-activity relationship study.