Identification of potential inhibitors of Schistosoma mansoni purine nucleoside phosphorylase from neolignan compounds using molecular modelling approaches

Abstract

Schistosomiasis is a parasitic disease that is part of the neglected tropical diseases (NTDs), which cause significant levels of morbidity and mortality in millions of people throughout the world. The enzyme purine nucleoside phosphorylase from Schistosoma mansoni (SmPNP) represents a potential target for discovering new agents, and neolignans stand out as an important class of compounds. In this work, molecular modeling studies and biological assays of a set of neolignans were conducted against the PNP enzymes of the parasite and the human homologue (HssPNP). The results of the molecular docking described that the neolignans showed good complementarity by the active site of SmPNP. Molecular dynamics (MD) studies revealed that both complexes (Sm/HssPNP - neolignan compounds) were stable by analyzing the root mean square deviation (RMSD) values, and the binding free energy values suggest that the selected structures can interact and inhibit the catalytic activity of the SmPNP. Finally, the biological assay indicated that the selected neolignans presented a better molecular profile of inhibition compared to the human enzyme, as these ligands did not have the capacity to inhibit enzymatic activity, indicating that these compounds are promising candidates and that they can be used in future research in chemotherapy for schistosomiasis.

Communicated by Ramaswamy H. Sarma

Keywords:

• Schistosomiasis
• purine nucleoside phosphorilase
• neolignans
• molecular docking
• molecular dynamics

Acknowledgements

We acknowledge the Quatro G Pesquisa & Desenvolvimento Ltda company to providing the human PNP enzyme.

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

The authors acknowledge the PROPESP/UFPA (Pró-Reitoria de Pesquisa e Pós-Graduação da UFPA) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) for the financial support and to improve the quality of this manuscript.