Synthesis of 1233A analogs and their inhibitory activity against hydroxymethylglutaryl coenzyme A synthase

T Sunazuka; K Tsuzuki; H Kumagai; H Tomoda; H Tanaka; H Nagashima; H Hashizume; S Omura

doi:10.7164/antibiotics.45.1139

Synthesis of 1233A analogs and their inhibitory activity against hydroxymethylglutaryl coenzyme A synthase

J Antibiot (Tokyo). 1992 Jul;45(7):1139-47. doi: 10.7164/antibiotics.45.1139.

Authors

T Sunazuka¹, K Tsuzuki, H Kumagai, H Tomoda, H Tanaka, H Nagashima, H Hashizume, S Omura

Affiliation

¹ Research Center for Biological Function, Kitasato Institute, Tokyo, Japan.

PMID: 1355474
DOI: 10.7164/antibiotics.45.1139

Abstract

Simple and efficient syntheses of 1233A analogs were developed and the inhibitory activity of the analogs against hydroxymethylglutaryl coenzyme A (HMG-CoA) synthase was determined. Study of the structure-activity relationships revealed that not only the geometry in beta-lactone moiety but also the length of the carbon side chain is important for inhibitory activity against HMG-CoA synthase.

MeSH terms

Animals
Fatty Acids, Unsaturated / chemical synthesis*
Fatty Acids, Unsaturated / pharmacology
Hydroxymethylglutaryl-CoA Synthase / antagonists & inhibitors*
Lactones / chemical synthesis*
Lactones / pharmacology
Mevalonic Acid / analogs & derivatives
Mevalonic Acid / pharmacology
Microbial Sensitivity Tests
Vero Cells / drug effects

Substances

Fatty Acids, Unsaturated
Lactones
antibiotic 1233A
mevalonolactone
Hydroxymethylglutaryl-CoA Synthase
Mevalonic Acid