•  
  •  
 

Abstract

Leishmaniasis is one of the most important endemic diseases in Sudan. The glycolytic pathway is one of the essential pathways in the survival and pathogenicity of the leishmania parasite. This study aimed to evaluate the antileishmanial activities of three antimalarial drugs through targeting the glycolytic pathway inside the parasite. Antileishmanial activities of artesunate, quinine and mefloquine were evaluated using an in vitro anti-promastigote assay. Then, in silico molecular docking was conducted using Autodock 4.0 software to study the molecular interactions of antimalarial drugs to different key glycolytic enzymes. The results of the current study, Artesunate, quinine, and mefloquine showed effective inhibitory activities against L. donovani with IC50 values of 58.85, 40.24, and 20.06 μg/ml, respectively. Molecular docking analysis revealed interesting interactions between different antimalarial drugs and various glycolytic enzymes (Glucose-6-phosphate isomerase, Triosephosphate isomerase, Glycerol-3-phosphate dehydrogenase, Glyceraldehyde-3-phosphate dehydrogenase and Pyruvate kinase). Moreover, these drugs interact with different amino acid residues of the proteins with satisfactory binding energies, particularly with artesunate. According to binding energies, Glycerol-3-phosphate dehydrogenase was represented the most potential target for three tested drugs. Collectively, our results showed promising antileishmanial activities of different antimalarial that may mediated through inhibition of glycolysis process in leishmania donovani promastigote.

Page

77

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.