Drug Design and Discovery Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan S7N 5C9, Canada.
Eur J Med Chem. 2010 Oct;45(10):4682-6. doi: 10.1016/j.ejmech.2010.07.030. Epub 2010 Jul 24.
A series of 2-(3-aryl-1-oxo-2-propenyl)-3-methylquinoxaline-1,4-dioxides 1a-l and 2-acetyl-3-methylquinoxaline-1,4-dioxide 2 were evaluated against Mycobacterium tuberculosis H(37)Rv. With the exception of the 4-nitro analog 1k, significant antitubercular potencies were observed in series 1 and 2 which have IC(50) values in the range of 1-23 microM. Negative correlations were noted between the IC(50) values of 1a-j, l towards M. tuberculosis and both the sigma and pi constants of the substituents in the benzylidene aryl ring. In particular, 1h emerged as a lead compound having IC(50) and IC(90) figures of 1.03 microM and 1.53 microM, respectively. This molecule affected respiration in rat liver mitochondria which is likely one way that 1h and the bioactive analogs exert their antitubercular properties. The quinoxaline 2, which lacks an alpha,beta-unsaturated group, has no effect on mitochondrial respiration using concentrations which inhibit the growth of M. tuberculosis.
一系列 2-(3-芳基-1-氧代-2-丙烯基)-3-甲基喹喔啉-1,4-二氧化物 1a-l 和 2-乙酰基-3-甲基喹喔啉-1,4-二氧化物 2 被评估了对结核分枝杆菌 H(37)Rv 的作用。除了 4-硝基类似物 1k 外，在系列 1 和 2 中观察到了显著的抗结核活性，其 IC(50) 值在 1-23 microM 的范围内。在 1a-j 和 l 对结核分枝杆菌的 IC(50) 值与苄叉芳环取代基的 sigma 和 pi 常数之间注意到了负相关性。特别是，1h 作为一种先导化合物出现，其 IC(50) 和 IC(90) 值分别为 1.03 microM 和 1.53 microM。该分子影响了大鼠肝线粒体的呼吸，这可能是 1h 和生物活性类似物发挥其抗结核特性的一种方式。缺乏α,β-不饱和基团的喹喔啉 2 在用抑制结核分枝杆菌生长的浓度下对线粒体呼吸没有影响。
