Research Article Open Access

In Silico and in Vitro Studies: Tryparedoxin Peroxidase Inhibitor Activity of Methotrexate for Antileishmanial Activity

Ravi Kumar Gundampati1, Shraddha Sahu2, Avinash Kumar Srivastava2, Sambamurthy Chandrasekaran3, Parameswara Rao Vuddanda2, Rajesh Kumar Pandey1, Radheshyam Maurya3, Sanjay Singh2 and Medicherla V. Jagannadham1
  • 1 Banaras Hindu University, India
  • 2 Indian Institute of Technology (BHU), India
  • 3 University of Hyderabad, India

Abstract

In order to understand the mechanism of molecular interactions at the active site of Tryparedoxin Peroxidase (Try P), homology modeling and docking studies were performed. We generated a Three-Dimensional (3D) model of target protein based on the Crystal structure of Leishmania Major Try PI (PDB ID: 3TUE) using modeler software. Docking analysis was carried out to study the effects of methotrexate on Tryparedoxin Peroxidase (Try P). Inhibition of the Tryparedoxin peroxidase interaction has become a new therapeutic strategy in treating leishmaniasis. Docking analysis was carried out to study the effects of methotrexate on Tryparedoxin Peroxidase (TryP). Tryparedoxin peroxidase of Trypanosomatidae family functions as antioxidant through their peroxidase and peroxynitrite reductase activities. The theoretical docking study, conducted on a sample previously reported for anti-cancer properties of Methotrexate at the binding site of 3D models of Tryparedoxin Peroxidase of Leishmania braziliensis (L. braziliensis Try P) examine interaction energy. Our studies indicate that Methotrexate displays potent activity against Try P with lowest binding energy and RMSD values to be -14.5879 Kcal/Mol and 2.0 A. The results of the present study clearly demonstrated the Tryparedoxin Peroxidase inhibitory activity by methotrexate in in silico docking analysis and in vitro assay which contributes towards understanding the mechanism of antileishmanial activity.

American Journal of Infectious Diseases
Volume 9 No. 4, 2013, 117-129

DOI: https://doi.org/10.3844/ajidsp.2013.117.129

Submitted On: 3 October 2013 Published On: 28 November 2013

How to Cite: Gundampati, R. K., Sahu, S., Srivastava, A. K., Chandrasekaran, S., Vuddanda, P. R., Pandey, R. K., Maurya, R., Singh, S. & Jagannadham, M. V. (2013). In Silico and in Vitro Studies: Tryparedoxin Peroxidase Inhibitor Activity of Methotrexate for Antileishmanial Activity. American Journal of Infectious Diseases, 9(4), 117-129. https://doi.org/10.3844/ajidsp.2013.117.129

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Keywords

  • Homology Modeling
  • Molecular Docking
  • Leishmania Braziliensis
  • Tryparedoxin Peroxidase
  • Methotrexate