涉及乙醇酸和乙醛酸衍生物对乙醇酸氧化酶抑制作用的定量构效关系。

Quantitative structure-activity relationships involving the inhibition of glycolic acid oxidase by derivatives of glycolic and glyoxylic acids.

作者信息

Randall W C, Streeter K B, Cresson E L, Schwam H, Michelson S R, Anderson P S, Cragoe E J, Williams H W, Eichler E, Rooney C S

出版信息

J Med Chem. 1979 Jun;22(6):608-14. doi: 10.1021/jm00192a002.

DOI:10.1021/jm00192a002

PMID:458816

Abstract

The enzyme glycolic acid oxidase oxidizes glycolate to glyoxylate and glyoxylate to oxalate. Three series of compounds related to the natural substrates, substituted glycolic, oxyacetic, and glyoxylic acids, have been investigated as inhibitors of this enzyme using the techniques of regression analysis and quantitative structure-activity relationships. The best overall correlation with inhibitory potencies was found with the Hansch hydrophobic parameter pi. The classical electronic parameters sigmap, sigmam, F, and R performed poorly. For the substituted glyoxylic acids, a dummy parameter relating to the presence of a nucleophilic group in close proximity to the alpha-carbonyl of the glyoxylate group was found to be highly significant. The syntheses of six novel glycolic and glyoxylic acids are described.

摘要

乙醇酸氧化酶可将乙醇酸氧化为乙醛酸，再将乙醛酸氧化为草酸。利用回归分析和定量构效关系技术，研究了与天然底物相关的三类化合物，即取代乙醇酸、羟基乙酸和乙醛酸，作为该酶的抑制剂。发现与抑制效力的最佳总体相关性与汉施疏水参数π有关。经典的电子参数σp、σm、F和R表现不佳。对于取代乙醛酸，发现一个与乙醛酸基团α-羰基附近亲核基团存在相关的虚拟参数具有高度显著性。描述了六种新型乙醇酸和乙醛酸的合成。