Supriya Khanra 1 , Subir Kumar Juin 2 , Junaid Jibran Jawed 3 , Sweta Ghosh 2 , Shreyasi Dutta 4 , Shaik Abdul Nabi 5 , Jyotirmayee Dash 6 , Dipak Dasgupta 4 , Subrata Majumdar 2 , * , Rahul Banerjee 1 , 7 , *
31 August 2020
Treatment failure and resistance to the commonly used drugs remains a major obstacle for successful chemotherapy against visceral leishmaniasis (VL). Since the development of novel therapeutics involves exorbitant costs, the effectiveness of the currently available antitrypanosomatid drug suramin has been investigated as an antileishmanial, specifically for VL, in vitro and in animal model experiments.
Leishmania donovani promastigotes were treated with suramin and studies were performed to determine the extent and mode of cell mortality, cell cycle arrest and other in vitro parameters. In addition, L. donovani infected BALB/c mice were administered suramin and a host of immunological parameters determined to estimate the antileishmanial potency of the drug. Finally, isothermal titration calorimetry (ITC) and enzymatic assays were used to probe the interaction of the drug with one of its putative targets namely parasitic phosphoglycerate kinase (LmPGK).
The in vitro studies revealed the potential efficacy of suramin against the Leishmania parasite. This observation was further substantiated in the in vivo murine model, which demonstrated that upon suramin administration, the Leishmania infected BALB/c mice were able to reduce the parasitic burden and also generate the host protective immunological responses. ITC and enzyme assays confirmed the binding and consequent inhibition of LmPGK due to the drug.
Visceral Leishmaniasis (VL) or Kala-azar, classed as a neglected tropical disease, is still a major problem worldwide, aggravated by increasing parasitic resistance against the drugs commonly used for its treatment. Since the development of novel therapeutics involves exorbitant costs, the effectiveness of the currently available antitrypanosomatid drug suramin has been investigated as an antileishmanial, specifically for VL, in vitro and in animal model experiments. Our study showed that suramin is effective against L. donovani and significantly reduced the (splenic/hepatic) parasitic burden in L. donovani infected BALB/c mice, switching the immune response in the infected BALB/c mice from T H2 to a T H1 type. The ITC data confirmed that suramin does indeed interact with parasitic phosphoglycerate kinase (LmPGK) and enzyme assays demonstrated the inhibition of LmPGK due to the drug. Therefore, our investigation raises the possibility of suramin being included in the repertoire of drugs used to treat VL.