Synthesis of new drug candidates to be tested against Micobacterium Tuberculosis


Synthesis of new drug candidates to be tested against Micobacterium Tuberculosis

Tuberculosis (TB), a contagious disease caused by Mycobacterium Tuberculosis (MTb), was considered a curable disease when, 50 years ago, several active anti-TB agents were discovered. A few years later, it became apparent that the use of these drugs as single agents led to rapid drug resistance among patients, and the treatment evolved to a multiple drug regimen for over 6-8 months. In the last decade, TB reappeared as a serious threat to public health, leading to a renewed interest in the active search for potential drug candidates with activity against MTb. In order to stimulate research in this area, the National Institute of Allergy and Infectious Diseases (NIAID) – USA, sponsored the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF), a service to investigators for screening new compounds supplied by the scientific community. We have recently signed a contract with this service and a list of some of the structures prepared in the last few years by our research group was submitted for evaluation. From these, ca. 400 new compounds were selected for biological tests. These compounds will be prepared again in a convenient scale and sent for testing after assessing their purity degree by elemental analysis and using IR, 1H and 13C NMR spectroscopy techniques.

Isoniazid was one of the first drugs introduced to treat TB. It is currently used in combination with other antimycobacterial agents, in a multi-drug regimen for TB therapy. Cycloserine and a number of quinolone drugs were initially developed as broad spectrum antibacterials and have also been used in the treatment of TB. Research will be conducted in order to combine Isoniazid or Cycloserin with purine derivatives or with fused heterocyclic structures analogous to quinolone antibiotics.

The nitroimidazopyran PA-824 has emerged as a potential drug candidate among several lead compounds that have recently been found. Inspired on its structure, new imidazole-based heterocycles will be prepared, where the nitro group (usually responsible for the toxicity of nitroimidazoles), will be replaced by a substituted triazole.

The synthesis of new drug candidates is the first step in a long and concerted effort to find lead compounds active against 


. In order to meet this goal, a significant increase in effort will be required at each stage of the drug discovery process, and this starts with the synthetic approach.

Universidade do Minho (UM)
Maria Fernanda Proença (PI) – CQUM
Alice Maria Dias – CQUM
Maria Alice Carvalho – CQUM
Filipe Areias – CQUM

  • Início e Fim

    2005-10-01 – 2009-03-01
  • Entidade Financiadora

    POCI/QUI/59356/2004 (Fase I) e PPCDT/QUI/59356/2004 (Fase II)
  • Financiamento

    Global - 28 006,00 EUR
  • Beneficiário Principal