Epohelmins A and B, novel lanosterol synthase inhibitors from a fungal strain FKI-0929.
From a fungal strain FKI-0929, two compounds designated epohelmins A and B, were isolated as new natural products with inhibitory activity against recombinant human lanosterol synthase. The crude extract from the whole broth of this strain was fractionated by silica gel column chromatography and HPLC to afford two isolated inhibitors. Detailed spectroscopic analyses led to the identification of their structures. They are diastereomers of 4,5-epoxy-2-(4'-oxoundec-(5'E)-enyl)-heptamethylenamines, and their relative stereochemical configurations were determined as (2R, 4R, 5R) or (2S, 4S, 5S) for epohelmin A, and (2R, 4S, 5R) or (2S, 4R, 5S) for epohelmin B, respectively. These compounds inhibited recombinant human lanosterol synthase with IC50 values of 10 and 6.0 microM, respectively.
Sakano
Yuichi
Y
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Shibuya
Masaaki
M
Yamaguchi
Yuichi
Y
Masuma
Rokuro
R
Tomoda
Hiroshi
H
Omura
Satoshi
S
Ebizuka
Yutaka
Y
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D005285:Fermentation; D005658:Fungi / Q000145:classification / Q000378:metabolism*; D006801:Humans; D019751:Intramolecular Transferases / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; C494514:epohelmin A; C494515:epohelmin B; D019751:Intramolecular Transferases; C021924:lanosterol synthase