Structure, derivatization, and antitumor activity of new griseusins from Nocardiopsis sp.

He J, Roemer E, Lange C, Huang X, Maier A, Kelter G, Jiang Y, Xu LH, Menzel KD, Grabley S, Fiebig HH, Jiang CL, Sattler I (2007) Structure, derivatization, and antitumor activity of new griseusins from Nocardiopsis sp. J Med Chem 50(21), 5168-5175.

Abstract

Four new griseusins, 4'-dehydro-deacetylgriseusin A (1) and 2a,8a-epoxy-epi-deacetylgriseusin B (2) as new constitutional derivatives and epi-deacetylgriseusin A (3) and epi-deacetylgriseusin B (4) as new stereoisomers, were isolated from Nocardiopsis sp. (YIM80133, DSM16644). 4'-Dehydro-deacetylgriseusin A (1) showed pronounced cytotoxic potency (mean IC50 = 0.430 microM) combined with a significant selectivity for mammary cancer, renal cancer, and melanoma in a panel consisting of 37 tumor cell lines. In a clonogenic assay with tumor cells from 51 solid tumors, 1 inhibited anchorage independent growth and in vitro colony formation of tumor cells in a concentration-dependent and tumor type selective manner. As 1 was only a minor product, a semisynthetic preparation from the major metabolite, epi-deacetylgriseusin A (3), was achieved. 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 synthetic isochromanequinone derivatives, which provided a basic structure-activity relationship study.

Leibniz-HKI-Authors

Klaus-Dieter Menzel

Identifier

doi: 10.1021/jm070170n

PMID: 17877337