Rational design of novel diketoacid-containing ferrocene inhibitors of HIV-1 integrase

被引:15
作者
da Silva, CHTP
Del Ponte, G
Neto, AF
Taft, CA
机构
[1] Ctr Brasileiro Pesquisas Fis, BR-22290180 Rio De Janeiro, Brazil
[2] Univ Sao Paulo, Dept Ciencias Farmaceut, Fac Ciencias Farmaceut, BR-14040903 Ribeirao Preto, Brazil
关键词
docking; density functional; molecular interaction field;
D O I
10.1016/j.bioorg.2005.03.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Molecular interaction field, density functional, and docking studies of novel potential ferrocene inhibitors of HIV-1 integrase (IN) are reported. The high docking scores, analysis of the ligand-receptor interactions in the active site as well as the molecular interaction potential calculations at the binding site of the receptor indicate important features for novel HIV-1 IN inhibitors. We also confirm in this work a novel binding trench in HIV-1 integrase, recently reported in a theoretical work by other authors. This observation may be interesting since the lack of detailed structural information about IN-ligand interactions has hampered the design of IN inhibitors. Our proposed ligands are open to experimental synthesis and testing. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:274 / 284
页数:11
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