LABADIE Guillermo Roberto
congresos y reuniones científicas
Novel Triazole drugs with potent anti-mycobacterial activity
LABADIE, GUILLERMO R.; DE LA IGLESIA, AGUSTINA; MORBIDONI, HERCTOR R.
Otro; IV Reunión de la SLAMTB; 2009
Sociedad Latinoamericana de Micobacterias y la tuberculosis
Human tuberculosis still is the most frequent infectious disease in the world, a fact worsened by the appearance of strains resistant to several drugs, known as Multi-drug resistant (MDR-TB) and Extremely Drug Resistant (XDR-TB). In that context, the quest for new drugs is a dramatic priority which as shown by programs aimed at identification of natural products, the re-evaluation of drugs used for treatment of other diseases (such as anti-psychotic drugs) and synthesis of compounds based on structural information provided by analysis of essential mycobacterial proteins. Interestingly, a recent report showed the anti-mycobacterial activity of azole drugs; although their mechanism of action is unknown this fact has triggered the use of azoles as a pharmacophore molecule. We here report the synthesis of a library of novel 1,2,3 -triazoles using a methodology known as click chemistry with the aim of finding new derivatives endowed with anti-mycobacterial activity. The compounds were assayed against several mycobacterial species including M. tuberculosis; as a result a molecule with a Minimum Inhibitory Concentration of 1μg/mL (thus three to five fold more active than Econazole) was found. The simplicity of the chemical procedure used allows for the synthesis of a high number of compounds, therefore we will use the compound selected through this work to make chemical modification in order to select a more powerful anti- tubercular molecule.