Differential inhibition of fungal oxidosqualene cyclase by 6E and 6Z isomers of 2,3‐epoxy‐10‐aza‐10,11‐dihydrosqualene

FEBS Letters

Milla, Paola¹  Carrano, Lùcia²  Ceruti, Maurizio¹  Balliano, Gianni¹  Viola, Franca¹  Cattel, Luigi¹ 

[1] Istituto di Chimica Farmaceutica Applicata, Corso Raffaello 31, 10125 Torino, Italy;Lepetit Research Center, MMDRI, Via R. Lepetit 34, 21040 Gerenzano, Varese, Italy

关键词: Oxidosqualene cyclase;    Sterol biosynthesis inhibitor;    Saccharomyces cerevisiae;    Candida albicans;   

DOI  :  10.1016/0014-5793(93)80586-J

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Inhibitory properties of 6E (compound 1) and 6Z (compound 2) isomers of 2,3-epoxy-10-aza-10,11-dihydrosqualene against oxidosqualene-lanosterol cyclase were assayed on microsomes and whole cells of Saccharomyces cerevisiae and Candida albicans. Only the 6E isomer (compound 1), bearing a correct substrate-like configuration, strongly inhibited the enzyme both in microsomes and cell cultures. The difference between compounds 1 and 2 (which had an unfavorable geometry) was especially evident when measuring [¹⁴C]acetate incorporation into non-saponifiable lipids extracted from treated cells. While isomer Z was totally ineffective at up to 30 μM, in cells treated with 5 μM isomer E, labelled oxidosqualene, the level of which was negligible in the control, rose to over 60% of the non-saponifiable lipids.

【 授权许可】

Unknown