Structure, derivatization, and antitumor activity of new griseusins from Nocardiopsis sp.
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.
He
Jian
J
Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Beutenbergstr. 11a, D-07745 Jena, Germany.
Roemer
Ernst
E
Lange
Corinna
C
Huang
Xueshi
X
Maier
Armin
A
Kelter
Gerhard
G
Jiang
Yi
Y
Xu
Li-Hua
LH
Menzel
Klaus-Dieter
KD
Grabley
Susanne
S
Fiebig
Heinz-Herbert
HH
Jiang
Cheng-Ling
CL
Sattler
Isabel
I
D039903:Actinobacteria / Q000737:chemistry*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008819:Mice, Nude; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D009368:Neoplasm Transplantation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D009285:Naphthoquinones; C012339:griseusin