新型多氧霉素衍生物的合成及其对白色念珠菌几丁质合酶的活性

Synthesis of new polyoxin derivatives and their activity against chitin synthase from Candida albicans.

作者信息

Emmer G, Ryder N S, Grassberger M A

出版信息

J Med Chem. 1985 Mar;28(3):278-81. doi: 10.1021/jm00381a003.

Abstract

Two analogues of L-alanylpolyoxin C with a modified peptide bond were synthesized and tested for inhibition of chitin synthase in Candida albicans. N-Methylation of the peptide bond (compound 13) or the replacement of it by NH2CH2 (compound 9) led to loss of activity in the enzyme assay. A novel analogue (compound 5) of nikkomycin was synthesized from uracil polyoxin C and (2S,3R)-3-hydroxyhomotyrosine, a component of echinocandin C. Despite high activity in the chitin synthase assay, 5 had no inhibitory effect on cells of C. albicans.

摘要

合成了两种肽键修饰的L-丙氨酰多氧菌素C类似物，并测试了它们对白色念珠菌几丁质合酶的抑制作用。肽键的N-甲基化（化合物13）或用NH2CH2取代肽键（化合物9）导致在酶测定中活性丧失。由尿嘧啶多氧菌素C和棘白菌素C的组分（2S，3R）-3-羟基高酪氨酸合成了一种新的多氧霉素类似物（化合物5）。尽管在几丁质合酶测定中活性很高，但5对白色念珠菌细胞没有抑制作用。