Interactions of 5-deazapteridine derivatives with Mycobacterium tuberculosis and with human dihydrofolate reductases.
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.
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
Elaine F F
EF
da Cunha
Teodorico
T
de Castro Ramalho
Ricardo
R
Bicca de Alencastro
Elaine Rose
ER
Maia
D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D015195:Drug Design; D005493:Folic Acid Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D008024:Ligands; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology*; D011487:Protein Conformation; D011621:Pteridines / Q000737:chemistry* / Q000494:pharmacology*; D013045:Species Specificity; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry* / Q000187:drug effects*; D013816:Thermodynamics
D000995:Antitubercular Agents; D005493:Folic Acid Antagonists; D008024:Ligands; D011621:Pteridines; D013762:Tetrahydrofolate Dehydrogenase