左炔诺孕酮的微生物羟基化作用。

The microbial hydroxylation of levonorgestrel.

作者信息

Choudhary Muhammad Iqbal, Atif Muhammad, Nawaz Sarfraz A, Fatmi Muhammad Qaiser

机构信息

HEJ Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi, Pakistan.

出版信息

Nat Prod Res. 2006 Oct;20(12):1074-81. doi: 10.1080/14786410500463411.

DOI:10.1080/14786410500463411

PMID:17201044

Abstract

The microbial transformation of levonorgestrel (1) by Cunningham elegans resulted in the formation of five hydroxylated metabolites, 13-ethyl-10beta, 17beta-dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one(2), 13-ethyl-6beta,17beta-dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one (3) 13-ethyl 6beta, 10beta, 17beta-trihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one (4) 13-ethyl-15alpha-17beta-dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one (5) and 13-ethyl-11alpha, 17beta-dihydroxy-18,19-dinor-17alpha-pregn-4en-20-yn-3-one. The fermentation of one with Rhizopus stolonifer, Fusarium lini and Curvularia lunata afforded compound 2 as a major metabolise. These metabolites were structurally characterized on the basis of spectroScopic techniques. Metabolite 6 was identified as a new compound. Compounds 2 2 ad 5 displayed inhibitory activity against the acetylcholinesterase ( AChE, EC. 3.1.1.7) with IC50 values of 79.2 and 24.5 microM, respectively. The metabolites 2 and 5 also showed inhibitory activity against the butyryLcholinesterase ( BChE, E.C 3.1.1.8) with IC50 values ranging between 9.4 and 309.8 microM.

摘要

秀丽隐杆线虫对左炔诺孕酮（1）的微生物转化产生了五种羟基化代谢产物，13 - 乙基 - 10β，17β - 二羟基 - 18,19 - 二去甲 - 17α - 孕 - 4 - 烯 - 20 - 炔 - 3 - 酮（2）、13 - 乙基 - 6β，17β - 二羟基 - 18,19 - 二去甲 - 17α - 孕 - 4 - 烯 - 20 - 炔 - 3 - 酮（3）、13 - 乙基 - 6β，10β，17β - 三羟基 - 18,19 - 二去甲 - 17α - 孕 - 4 - 烯 - 20 - 炔 - 3 - 酮（4）、13 - 乙基 - 15α - 17β - 二羟基 - 18,19 - 二去甲 - 17α - 孕 - 4 - 烯 - 20 - 炔 - 3 - 酮（5）和13 - 乙基 - 11α，17β - 二羟基 - 18,19 - 二去甲 - 17α - 孕 - 4 - 烯 - 20 - 炔 - 3 - 酮。用匍枝根霉、亚麻镰刀菌和新月弯孢霉对其进行发酵，得到化合物2作为主要代谢产物。这些代谢产物通过光谱技术进行了结构表征。代谢产物6被鉴定为一种新化合物。化合物2和5对乙酰胆碱酯酶（AChE，EC. 3.1.1.7）具有抑制活性，IC50值分别为79.2和24.5微摩尔。代谢产物2和5对丁酰胆碱酯酶（BChE，E.C 3.1.1.8）也表现出抑制活性，IC50值在9.4至309.8微摩尔之间。