کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4752570 | 1416276 | 2017 | 10 صفحه PDF | دانلود رایگان |
- Growing resistance in malarial parasites, particularly in Plasmodium falciparum needs for development of novel drug targets.
- Inosine monophosphate dehydrogenase (IMPDH) is an important target for antimalarial drug discovery.
- A homology model for P. falciparum IMPDH was constructed taking human IMPDH (PDB code 1NF7) as template.
- Combinatorial library of ribavirin (RVP) derivatives (1347 molecules) was designed.
- A total of five ribavirin derivatives were identified having greater binding affinity with Plasmodium falciparum IMPDH.
Growing resistance in malarial parasites, particularly in Plasmodium falciparum needs a serious search for the discovery of novel drug targets. Inosine monophosphate dehydrogenase (IMPDH) is an important target for antimalarial drug discovery process in P. falciparum for the treatment of malaria. In the absence of x-ray crystal structure of this enzyme, homology modeling proved to be a reasonable alternate to study substrate binding mechanisms of this enzyme. In this study, a 3-D homology model for P. falciparum IMPDH was constructed taking human IMPDH (PDB code 1NF7) as template. Furthermore, an in-silico combinatorial library of ribavirin (RVP) derivatives (1347 molecules) was designed and virtually screened for ligands having selectively greater binding affinity with Plasmodium falciparum IMPDH relative to human IMPDH II. A total of five Ribavirin derivatives were identified as having greater binding affinity (â126 to â108Â Kcal/mol and â9.4 to â8.6Â Kcal/mol) with Plasmodium falciparum IMPDH. These five inhibitors should be used as selective and potent for Plasmodium falciparum IMPDH. Such type of study will provide information to synthetic medicinal chemist to enhance the potential of compounds (RVP derivatives) as chemotherapeutic agents to fight against the increasing burden of malarial infections.
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Journal: Computational Biology and Chemistry - Volume 71, December 2017, Pages 10-19