Purine salvage pathway in Mycobacterium tuberculosis

Rodrigo G. Ducati, A. Breda, L. A. Basso, D. S. Santos

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Millions of deaths worldwide are caused by the aetiological agent of tuberculosis, Mycobacterium tuberculosis. The increasing prevalence of this disease, the emergence of drug-resistant strains, and the devastating effect of human immunodeficiency virus coinfection have led to an urgent need for the development of new and more efficient antimycobacterial drugs. The modern approach to the development of new chemical compounds against complex diseases, especially the neglected endemic ones, such as tuberculosis, is based on the use of defined molecular targets. Among the advantages, this approach allows (i) the search and identification of lead compounds with defined molecular mechanisms against a specific target (e.g. enzymes from defined pathways), (ii) the analysis of a great number of compounds with a favorable cost/benefit ratio, and (iii) the development of compounds with selective toxicity. The present review describes the enzymes of the purine salvage pathway in M. tuberculosis as attractive targets for the development of new antimycobacterial agents. Enzyme kinetics and structural data have been included to provide a thorough knowledge on which to base the search for compounds with biological activity. We have focused on the mycobacterial homologues of this pathway as potential targets for the development of new antitubercular agents.

Original languageEnglish (US)
Pages (from-to)1258-1275
Number of pages18
JournalCurrent Medicinal Chemistry
Volume18
Issue number9
DOIs
StatePublished - Mar 2011
Externally publishedYes

Fingerprint

Salvaging
Mycobacterium tuberculosis
Antitubercular Agents
Lead compounds
Enzyme kinetics
Chemical compounds
Tuberculosis
Enzymes
Bioactivity
Viruses
Pharmaceutical Preparations
Neglected Diseases
Toxicity
Anti-Bacterial Agents
Coinfection
Cost-Benefit Analysis
HIV
Costs
purine

Keywords

  • Crystallographic structures
  • Enzyme kinetics
  • Mycobacterium tuberculosis
  • Nucleotide metabolism
  • Purine salvage pathway
  • Rational drug design
  • Selective toxicity
  • Tuberculosis

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Ducati, R. G., Breda, A., Basso, L. A., & Santos, D. S. (2011). Purine salvage pathway in Mycobacterium tuberculosis. Current Medicinal Chemistry, 18(9), 1258-1275. https://doi.org/10.2174/092986711795029627

Purine salvage pathway in Mycobacterium tuberculosis. / Ducati, Rodrigo G.; Breda, A.; Basso, L. A.; Santos, D. S.

In: Current Medicinal Chemistry, Vol. 18, No. 9, 03.2011, p. 1258-1275.

Research output: Contribution to journalArticle

Ducati, RG, Breda, A, Basso, LA & Santos, DS 2011, 'Purine salvage pathway in Mycobacterium tuberculosis', Current Medicinal Chemistry, vol. 18, no. 9, pp. 1258-1275. https://doi.org/10.2174/092986711795029627
Ducati, Rodrigo G. ; Breda, A. ; Basso, L. A. ; Santos, D. S. / Purine salvage pathway in Mycobacterium tuberculosis. In: Current Medicinal Chemistry. 2011 ; Vol. 18, No. 9. pp. 1258-1275.
@article{51a3ea7fba704f9b811d0ed6b0080610,
title = "Purine salvage pathway in Mycobacterium tuberculosis",
abstract = "Millions of deaths worldwide are caused by the aetiological agent of tuberculosis, Mycobacterium tuberculosis. The increasing prevalence of this disease, the emergence of drug-resistant strains, and the devastating effect of human immunodeficiency virus coinfection have led to an urgent need for the development of new and more efficient antimycobacterial drugs. The modern approach to the development of new chemical compounds against complex diseases, especially the neglected endemic ones, such as tuberculosis, is based on the use of defined molecular targets. Among the advantages, this approach allows (i) the search and identification of lead compounds with defined molecular mechanisms against a specific target (e.g. enzymes from defined pathways), (ii) the analysis of a great number of compounds with a favorable cost/benefit ratio, and (iii) the development of compounds with selective toxicity. The present review describes the enzymes of the purine salvage pathway in M. tuberculosis as attractive targets for the development of new antimycobacterial agents. Enzyme kinetics and structural data have been included to provide a thorough knowledge on which to base the search for compounds with biological activity. We have focused on the mycobacterial homologues of this pathway as potential targets for the development of new antitubercular agents.",
keywords = "Crystallographic structures, Enzyme kinetics, Mycobacterium tuberculosis, Nucleotide metabolism, Purine salvage pathway, Rational drug design, Selective toxicity, Tuberculosis",
author = "Ducati, {Rodrigo G.} and A. Breda and Basso, {L. A.} and Santos, {D. S.}",
year = "2011",
month = "3",
doi = "10.2174/092986711795029627",
language = "English (US)",
volume = "18",
pages = "1258--1275",
journal = "Current Medicinal Chemistry",
issn = "0929-8673",
publisher = "Bentham Science Publishers B.V.",
number = "9",

}

TY - JOUR

T1 - Purine salvage pathway in Mycobacterium tuberculosis

AU - Ducati, Rodrigo G.

AU - Breda, A.

AU - Basso, L. A.

AU - Santos, D. S.

PY - 2011/3

Y1 - 2011/3

N2 - Millions of deaths worldwide are caused by the aetiological agent of tuberculosis, Mycobacterium tuberculosis. The increasing prevalence of this disease, the emergence of drug-resistant strains, and the devastating effect of human immunodeficiency virus coinfection have led to an urgent need for the development of new and more efficient antimycobacterial drugs. The modern approach to the development of new chemical compounds against complex diseases, especially the neglected endemic ones, such as tuberculosis, is based on the use of defined molecular targets. Among the advantages, this approach allows (i) the search and identification of lead compounds with defined molecular mechanisms against a specific target (e.g. enzymes from defined pathways), (ii) the analysis of a great number of compounds with a favorable cost/benefit ratio, and (iii) the development of compounds with selective toxicity. The present review describes the enzymes of the purine salvage pathway in M. tuberculosis as attractive targets for the development of new antimycobacterial agents. Enzyme kinetics and structural data have been included to provide a thorough knowledge on which to base the search for compounds with biological activity. We have focused on the mycobacterial homologues of this pathway as potential targets for the development of new antitubercular agents.

AB - Millions of deaths worldwide are caused by the aetiological agent of tuberculosis, Mycobacterium tuberculosis. The increasing prevalence of this disease, the emergence of drug-resistant strains, and the devastating effect of human immunodeficiency virus coinfection have led to an urgent need for the development of new and more efficient antimycobacterial drugs. The modern approach to the development of new chemical compounds against complex diseases, especially the neglected endemic ones, such as tuberculosis, is based on the use of defined molecular targets. Among the advantages, this approach allows (i) the search and identification of lead compounds with defined molecular mechanisms against a specific target (e.g. enzymes from defined pathways), (ii) the analysis of a great number of compounds with a favorable cost/benefit ratio, and (iii) the development of compounds with selective toxicity. The present review describes the enzymes of the purine salvage pathway in M. tuberculosis as attractive targets for the development of new antimycobacterial agents. Enzyme kinetics and structural data have been included to provide a thorough knowledge on which to base the search for compounds with biological activity. We have focused on the mycobacterial homologues of this pathway as potential targets for the development of new antitubercular agents.

KW - Crystallographic structures

KW - Enzyme kinetics

KW - Mycobacterium tuberculosis

KW - Nucleotide metabolism

KW - Purine salvage pathway

KW - Rational drug design

KW - Selective toxicity

KW - Tuberculosis

UR - http://www.scopus.com/inward/record.url?scp=79952804465&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952804465&partnerID=8YFLogxK

U2 - 10.2174/092986711795029627

DO - 10.2174/092986711795029627

M3 - Article

C2 - 21366536

AN - SCOPUS:79952804465

VL - 18

SP - 1258

EP - 1275

JO - Current Medicinal Chemistry

JF - Current Medicinal Chemistry

SN - 0929-8673

IS - 9

ER -