PubMed · 14689926
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Bob Huff. 2003. TB treatment evolves.. https://pubmed.ncbi.nlm.nih.gov/14689926/
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Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a leading cause of mortality worldwide into 21st century. The mortality and spread of this disease has further been aggravated because of synergy of this disease with HIV. A number of anti-TB drugs are ineffective against this disease because of development of resistance strains. Internationally efforts are being made to develop new anti-tubercular agents. A number of drug targets from cell wall biosynthesis, nucleic acid biosynthesis, and many other biosynthetic pathways are being unraveled throughout the world and are being utilized for drug development. In this review, socioeconomic problems in developing countries, efforts to control this disease in different individuals, the targets (known already and newly discovered), existing anti-tubercular agents including natural products and lead molecules, and the future prospects to develop new anti-TB agents are described.
A series of 2-sulfonamido/trifluoromethyl-6-(4'-substituted aryl/heteroaryl)imidazo[2,1-b]-1,3,4-thiadiazole derivatives (II) have been synthesized by reaction of 2-amino-5-sulfonamido/trifluoromethyl-1,3,4-thiadiazoles and an appropriate alpha-haloaryl/heteroaryl ketones. Further 5-bromo (III), 5-thiocyanato (IV), 5-gaunylhydrazone (V) derivatives were synthesized in order to study the effect of these substituents on biological activity. Structures of these compounds were established by IR, (1)H NMR, (13)C NMR, Mass and HRMS. The selected compounds were evaluated for their preliminary in vitro anti-tuberculosis activity against Mycobacterium tuberculosis H37Rv strain using radiometric BACTEC and broth dilution assay methods. The results show that compounds 5, 7, 8, 10 and 12 exhibited moderate to good anti-tubercular activity with percentage inhibition of 29, 43, 58, 31 and 41, respectively, at a MIC of >6.25 microg/mL. Compound 18 showed a MIC of 20 microg/mL.
Mycobacteria biosynthesize a cell wall structure that is rich in polysaccharides containing arabinofuranose residues. The source of these arabinofuranose residues is decaprenolphosphoarabinose (1), the donor substrate for mycobacterial arabinosyltransferases. We have previously demonstrated that an analog of 1, C-phosphonate 7, prevented the growth of mycobacteria and this compound is currently undergoing testing for efficacy in tuberculosis-infected mice. We describe here the synthesis and testing of additional analogs of 1 that contain either a sulfone (8-14) or phosphinic acid (15-19) moiety in place of the phosphodiester functionality. Screening of these compounds in vitro against Mycobacterium tuberculosis strain H(37)Rv revealed that while some of these compounds possessed low to modest activity, none was as potent as 7.