Investigation of the efficacy of identified acetolactate synthase inhibitors, peptidyl cysteine protease inhibitors, thiolactomycins, and thiosemicarbazone compounds against Mycobacterium tuberculosis
type: CreativeWork
description: Tuberculosis remains an important public health problem worldwide. There has been increase in the development of drug resistance towards INH and RIF, two of the frontline antimycobacterial drugs currently used in therapeutic regimes. As an attempt to address drug resistance, the World Health Organization has implemented the DOTS strategy in 182 countries. Moreover, new chemical libraries of potential antituberculosis drugs have been designed and synthesised. We therefore assessed 121 derivatives from the acetolactate synthase inhibitors, cysteine protease inhibitors, thiosemicarbazones, and thiolactomycins classes of compounds for in vitro efficacy against M. tuberculosis using the resazurin microtitre plate assay afterwhich active compounds were assessed for cytotoxicity in vitro against elicited peritoneal macrophages using the MTT assay. Of the 38 acetolactate synthase inhibitors tested, 2 derivatives namely RKG162A and RKG1541 were bactericidal against M. tuberculosis. Both derivatives were mildly cytotoxic against macrophages. For cysteine protease inhibitors, 35 derivatives were tested. Four derivatives namely AXE1, AXE4, AXE5, and AXE29 were bactericidal whereas AXE2, AXE3, AXE35, and NAT47 were bacteriostatic.
abstract: Tuberculosis remains an important public health problem worldwide. There has been increase in the development of drug resistance towards INH and RIF, two of the frontline antimycobacterial drugs currently used in therapeutic regimes. As an attempt to address drug resistance, the World Health Organization has implemented the DOTS strategy in 182 countries. Moreover, new chemical libraries of potential antituberculosis drugs have been designed and synthesised. We therefore assessed 121 derivatives from the acetolactate synthase inhibitors, cysteine protease inhibitors, thiosemicarbazones, and thiolactomycins classes of compounds for in vitro efficacy against M. tuberculosis using the resazurin microtitre plate assay afterwhich active compounds were assessed for cytotoxicity in vitro against elicited peritoneal macrophages using the MTT assay. Of the 38 acetolactate synthase inhibitors tested, 2 derivatives namely RKG162A and RKG1541 were bactericidal against M. tuberculosis. Both derivatives were mildly cytotoxic against macrophages. For cysteine protease inhibitors, 35 derivatives were tested. Four derivatives namely AXE1, AXE4, AXE5, and AXE29 were bactericidal whereas AXE2, AXE3, AXE35, and NAT47 were bacteriostatic.
author: Sebesho, Biopelo Felicity
language: eng
date published: 2006
date modified: 2026-07-22T22:23:34Z
provider: University of Cape Town
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Division of Immunology

PropertyValue
property ID: Handle
value: http://hdl.handle.net/11427/3116