Evaluation of antileishmanial activity of valproic acid against Leishmania donovani: An integrated in silico and in vitro study

Authors

  • Mohamed A. A. Elbadawi Department of Pharmacology, Faculty of Pharmacy, University of Khartoum, Khartoum 11111, Sudan
  • Mohamed K. A. Awadalla College of Pharmacy, University of Hail, Hail 81451, Saudi Arabia
  • Marwa S. S. Osman Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Khartoum and Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ahfad University for Women, Khartoum 11111, Sudan
  • Magdi A. Mohamed Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Khartoum, Khartoum 11111, Sudan
  • Mahmoud M. E. Mudawi Department of Pharmacology and Toxicology, Faculty of Pharmacy, Northern Border University, Rafha, Saudi Arabia and Department of Pharmacology, Faculty of Pharmacy, Omdurman Islamic University, Omdurman, Sudan
  • Muzamil M. Abdel Hamid Department of Parasitology and Medical Entomology, Institute of Endemic Diseases, University of Khartoum, Khartoum 11111, Sudan
  • Malik S. Mohamed Department of Pharmaceutics, Faculty of Pharmacy, University of Khartoum, Khartoum 11111, Sudan
  • Mohammed A. Gafar Department of Pharmaceutics, Faculty of Pharmacy, University of Khartoum, Khartoum 11111, Sudan

Keywords:

LdHDAC1, leishmania, valproic acid, amphotericin B, histone deacetylase inhibitor, homology model, drug-repurposing

Abstract

The antileishmanial activity of valproic acid was evaluated in an in vitro culture of Leishmania donovani promastigotes using amphotericin B as standard. Both valproic acid and amphotericin B showed antileishmanial activity at IC50s of 0.183 and 0.138 μg/ml, respectively. A homology model of Leishmania donovani histone deacetylase I (LdHDACI) was built and validated using in silico tools. Docking valproic acid into the active site of this Zn–dependent LdHDACI added a bidentate coordination to the tricoordinated metal. The resultant pentacordinated Zn+2 is no longer available for the natural substrate. Thus, the antileishmanial mechanism of valporic acid is thought to be via competitive inhibition of LdHDACI.

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Published

2016-01-30

How to Cite

Mohamed A. A. Elbadawi, Mohamed K. A. Awadalla, Marwa S. S. Osman, Magdi A. Mohamed, Mahmoud M. E. Mudawi, Muzamil M. Abdel Hamid, Malik S. Mohamed, & Mohammed A. Gafar. (2016). Evaluation of antileishmanial activity of valproic acid against Leishmania donovani: An integrated in silico and in vitro study. World Journal of Pharmaceutical Sciences, 4(2), 153–159. Retrieved from https://wjpsonline.com/index.php/wjps/article/view/antileishmanial-valproic-acid-leishmania-donovani

Issue

World J Pharm Sci 2016; 4(2): 148-275

Section

Research Article

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