Novel spirodihydrobenzofuranlactams as antagonists of endothelin and as inhibitors of HIV-1 protease produced by Stachybotrys Sp. I. Fermentation, isolation and biological activity.
Six novel spirodihydrobenzofuranlactams I - VI (1 - 6) and a related spirodihydrobenzofuranalcohol, the previously described natural compound L-671,776 (7), were isolated from cultures of two different Stachybotrys species. These secondary metabolites showed antagonistic effects in the endothelin receptor binding assay and inhibited HIV-1 protease. Both biological activities are novel for L-671,776 (7). The pseudosymmetric spirodihydrobenzofuranlactam VI (6) is the most potent representative of this class of compounds exhibiting IC50 values of 1.5 microM in the ET-A receptor binding assay and 11 microM in the HIV-1 protease inhibition assay.
Roggo
B E
BE
Core Drug Discovery Technologies, Pharmaceutical Division, Ciba-Geigy Limited, Basel, Switzerland.
Petersen
F
F
Sills
M
M
Roesel
J L
JL
Moerker
T
T
Peter
H H
HH
D000818:Animals; D016232:Endothelins / Q000037:antagonists & inhibitors*; D005285:Fermentation; D017320:HIV Protease Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D007769:Lactams / Q000302:isolation & purification* / Q000494:pharmacology; D051381:Rats; D013191:Stachybotrys / Q000378:metabolism*
D016232:Endothelins; D017320:HIV Protease Inhibitors; D007769:Lactams