E-2-3-(34-Dichlorophenyl)-1-oxo-2-propenyl-3-methylquinoxaline-14-dioxide: A lead antitubercular agent which alters mitochondrial respiration in rat liver

摘要

A series of 2-(3-aryl-1-oxo-2-propenyl)-3-methylquinoxaline-1,4-dioxides >1a–>l and 2-acetyl-3-methyl-quinoxaline-1,4-dioxide >2 were evaluated against Mycobacterium tuberculosis H37Rv. With the exception of the 4-nitro analog >1k, significant antitubercular potencies were observed in series >1 and >2 which have IC50 values in the range of 1–23 μM. Negative correlations were noted between the IC50 values of >1a–>j, >l towards M. tuberculosis and both the σ and π constants of the substituents in the benzylidene aryl ring. In particular, >1h emerged as a lead compound having IC50 and IC90 figures of 1.03 μM and 1.53 μM, 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 α,β-unsaturated group, has no effect on mitochondrial respiration using concentrations which inhibit the growth of M. tuberculosis.