253
Views
11
CrossRef citations to date
0
Altmetric
Research Article

Identification of two natural compound inhibitors of Leishmania donovani Spermidine Synthase (SpdS) through molecular docking and dynamic studies

, &
Pages 2678-2693 | Received 18 May 2017, Accepted 06 Aug 2017, Published online: 05 Sep 2017
 

Abstract

Visceral leishmaniasis caused by the protozoan Leishmania donovani is the most severe form of leishmaniasis and it is potentially lethal if untreated. Despite the availability of drugs for treating the disease, the current drug regime suffers from drawbacks like antibiotic resistance and toxicity. New drugs have to be discovered in order to overcome these limitations. Our aim is to identify natural compounds from plant sources as putative inhibitors considering the occurrence of structural diversity in plant sources. Spermidine Synthase (SpdS) was chosen as the target enzyme as it plays a vital role in growth, survival, and due to its contribution in virulence. Our initial investigation started with a literature survey in identifying natural compounds that showed antileishmanial activity. Subsequently, we identified two monoterpenoid compounds, namely Geraniol and Linalool, that were structurally analogous to one of the substrates (putrescine) of SpdS. In the present study, homology model of L. donovani SpdS was generated and the binding affinity of the identified compounds was analyzed and also compared with the putrescine through molecular docking and dynamic studies. The pharmacokinetic properties of the identified compounds were validated and the binding efficiency of these ligands over the original substrate has been demonstrated. Based on these studies, Geraniol and Linalool can be considered as lead molecules for future investigations targeting SpdS. This study further emphasizes the choice of natural compounds as a good source of therapeutic agents.

Acknowledgments

KP and VKD gratefully acknowledge the Department of Biotechnology (DBT), Government of India for the financial support in the form of grant under North Eastern Region Twinning Programme.

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 61.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 1,074.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.