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

Author : 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

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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