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Docking-based screening of natural product database in quest for dual site inhibitors of Trypanosoma cruzi trypanothione reductase (TcTR)

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Abstract

Chagas disease is caused by the protozoan Trypanosoma cruzi prevalent in the endemic regions of Latin American countries. With the existing drugs having severe toxic side effects, neither a vaccine nor an effective treatment is available for this chronic disease till date. In a pursuit to develop novel drug candidates against Chagas disease, we looked at the vast reservoir of mother nature and built an in-house library of 110 natural plant metabolites from medicinal plants having proven trypanocidal activities. This battery of compounds was examined against T. cruzi trypanothione reductase (1GXF) via computational methods using Autodock. 18-acetoxy-5,6-deoxy-5-withenolide (B.E. = −11.05 kcal/mol) and Sarachine (B.E. = −10.86 kcal/mol) turned out to be the top scorers in this study. Further pharmacophore detection of the high scorers resulted in a hybrid model considering the structural and spatial characteristics of the molecules. This can be further used to generate promising drug candidates aligned for clinical development in the drug design pipeline.

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Acknowledgments

The authors are grateful to CSIR (Grant No. CSR-724-CMD) for financial support. One of the authors (D.S.) is thankful to MHRD for the award of fellowship.

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  1. Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee, 247667, India

    Debasmita Saha & Anuj Sharma

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  1. Debasmita Saha
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  2. Anuj Sharma
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Correspondence to Anuj Sharma.

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Saha, D., Sharma, A. Docking-based screening of natural product database in quest for dual site inhibitors of Trypanosoma cruzi trypanothione reductase (TcTR). Med Chem Res 24, 316–333 (2015). https://doi.org/10.1007/s00044-014-1122-x

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  • DOI: https://doi.org/10.1007/s00044-014-1122-x

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