机构:
So Res Inst, Drug Discovery Div, Birmingham, AL 35255 USA
So Res Inst, Drug Dev Div, Birmingham, AL 35255 USAUniv Fed Lavras UFLA, Dept Quim, BR-37200000 Lavras, MG, Brazil
There are major differences between the structures of human dihydrofolate reductase (hD-HFR) and Mycobacterium tuberculosis dihydrofolate reductase (mtDHFR). These differences may allow the design of more selective mtDHFR inhibitors. In this paper, we have used docking approaches to study the binding orientations and predict binding affinities of 2,4-diamino-5-methyl-5-deazapteridines derivatives in both hDHFR and mtDHFR. Our results of molecular docking combined with experimental data for inhibition of the human and mycobacterial dihydrofolate reductases suggest the presence of empty spaces around the 2,4-diaminodeazapteridine and N-10-phenyl rings in the mtDHFR active site that are not found in the hDHFR-bound structures. Preparation of new analogs with substituents attached to C7 of the pteridine nucleus and positions 3 and 4 of the N-10-phenyl group should increase the affinity and selectivity for mtDHFR.
机构:
Fed Univ Rio De Janeiro, Inst Quim, Dept Quim Organ, BR-21949900 Rio De Janeiro, BrazilFed Univ Rio De Janeiro, Inst Quim, Dept Quim Organ, BR-21949900 Rio De Janeiro, Brazil
da Cunha, EFF
Ramalho, TC
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Fed Univ Rio De Janeiro, Inst Quim, Dept Quim Organ, BR-21949900 Rio De Janeiro, BrazilFed Univ Rio De Janeiro, Inst Quim, Dept Quim Organ, BR-21949900 Rio De Janeiro, Brazil
Ramalho, TC
Mala, ER
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Fed Univ Rio De Janeiro, Inst Quim, Dept Quim Organ, BR-21949900 Rio De Janeiro, BrazilFed Univ Rio De Janeiro, Inst Quim, Dept Quim Organ, BR-21949900 Rio De Janeiro, Brazil
Mala, ER
de Alencastro, RB
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机构:
Fed Univ Rio De Janeiro, Inst Quim, Dept Quim Organ, BR-21949900 Rio De Janeiro, BrazilFed Univ Rio De Janeiro, Inst Quim, Dept Quim Organ, BR-21949900 Rio De Janeiro, Brazil
机构:
Fed Univ Rio De Janeiro, Inst Quim, Dept Quim Organ, BR-21949900 Rio De Janeiro, BrazilFed Univ Rio De Janeiro, Inst Quim, Dept Quim Organ, BR-21949900 Rio De Janeiro, Brazil
da Cunha, EFF
Ramalho, TC
论文数: 0引用数: 0
h-index: 0
机构:
Fed Univ Rio De Janeiro, Inst Quim, Dept Quim Organ, BR-21949900 Rio De Janeiro, BrazilFed Univ Rio De Janeiro, Inst Quim, Dept Quim Organ, BR-21949900 Rio De Janeiro, Brazil
Ramalho, TC
Mala, ER
论文数: 0引用数: 0
h-index: 0
机构:
Fed Univ Rio De Janeiro, Inst Quim, Dept Quim Organ, BR-21949900 Rio De Janeiro, BrazilFed Univ Rio De Janeiro, Inst Quim, Dept Quim Organ, BR-21949900 Rio De Janeiro, Brazil
Mala, ER
de Alencastro, RB
论文数: 0引用数: 0
h-index: 0
机构:
Fed Univ Rio De Janeiro, Inst Quim, Dept Quim Organ, BR-21949900 Rio De Janeiro, BrazilFed Univ Rio De Janeiro, Inst Quim, Dept Quim Organ, BR-21949900 Rio De Janeiro, Brazil