Docking and biological activity of pteridine analogs: search for inhibitors of pteridine reductase enzymes from Trypanosoma cruzi

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• 作者：Schormann ; Norbert ; Senkovich ; Olga ; Ananthan ; Subramaniam ; Chattopadhyay ; Debasish
• 关键词：Chagas' disease ; Pteridine reductase 1 ; Pteridine reductase 2 ; Dihydrofolate reductase ; Docking
• 刊名：Journal of Molecular Structure: THEOCHEM
• 出版年：2003
• 出版时间：September 18, 2003
• 年：2003
• 卷：635
• 期：1-3
• 页码：37-44
• 全文大小：234 K

文摘

The program DOCK4.0 was used to predict and evaluate the binding mode for a set of inhibitors from a compound library of pteridine analogs against Trypanosoma cruzi pteridine reductase 2 (TcPTR2). The docked ligand conformations are, as expected, similar to the observed binding mode of MTX in the crystal structure of the TcPTR2 inhibitor complex. Dock energy scores are correlated with experimental enzymatic activity data (K_i) and calculated binding affinities (K_d) for these inhibitors. The screened compounds showed activity comparable to MTX in enzyme assays. An initial attempt is made to correlate the structure of these compounds to their affinity.