MINIMALIST SCAFFOLD OF TRIAZOLYL-PRENYLATED COMPOUNDS: TOWARD NEW MODULATED ANTIPARASITIC AGENTS

LUCÍA FARGNOLI; BABU TEKWANI; EXEQUIEL O. J. PORTA; ISABEL NOCITO; GUILLERMO R. LABADIE; YAZMÍN SANTOS; ESTEBAN SERRA

Buzios

Simposio; BrazMedChem 2016; 2016

Sociedade Brasileira de Química

One of seven people in the world is affected by Neglected Tropical Diseases (NTDs). Treatments of these diseases are insufficient and inefficient and require constant development of new drugs and strategies. Within the universe of small organic molecules, the isoprenoids are the most important and numerous families of metabolites. In this regard, it is useful to focus on the design, synthesis and studies of molecular probes that interfere with different biosynthetic routes, particularly the isoprene and sterol pathways. Previously our group has prepared a library of prenyl-decorated 1,2,3-triazolyl-sterols. Members of that collection shown excellent in vitro antiparasitic activities against the etiological agents of different diseases of high impact on humans health.Inspired on active isoprenyl-1,2,3,triazolyl sterols, a minimalistic design was proposed keeping the 1,2,3-triazolyl-isoprenyl moiety (as possible pharmacofore). A collection of analogs was prepared with different number of isoprenic units, varying the regiochemistry of the first isoprenic unit. The steriod was replaced by small hidrophobic groups. All the compounds were tested against the parasites responsible of the malaria (P. falciparum chloroquine sensitive and resistant strains), visceral leishmaniasis (L. donovani), HAT (T. brucei (T. cruzi). Our strategy also included action mechanism studies of the lead compounds and in silico ADME-Tox.