Instituto de Quimica da Universidade Federal do Rio de Janeiro--UFRJ, Departamento de Quimica Organica, Centro de Tecnologia-Bl A-Sala 609, Ilha do Fundao, Rio de Janeiro, CEP 21949-900 - RJ--Brazil. elaine@iq.ufrj.br
Abstract:
There are major differences between the structures of human dihydrofolate reductase (hDHFR) and Mycobacterium tuberculosis dihydrofolate reductase (mtDHFR). These differences may allow us to design more selective mtDHFR inhibitors. In this paper we study the reactions of six different compounds derived from 5-deazapteridine with human and bacterial enzymes. Results suggest that the addition of hydrophobic groups to the aminophenyl ring would increase mtDHFR-inhibitor affinity and selectivity.