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