Chalcones as a Basis for Computer-Aided Drug Design: Innovative Approaches to Tackle Malaria
Marilia NN Lima, Bruno Junior Neves, Gustavo Capatti Cassiano, Marcelo do Nascimento Gomes, Kaira Cristina Peralis Tomaz, Letícia Tiburcio Ferreira, Tatyana Almeida Tavella, Juliana Calit, Daniel Y. Bargieri, Eugene N. Muratov, Fábio Trindade Maranhão Costa, Carolina Horta Andrade · Future Medicinal Chemistry · 2019
Aim: Computer-aided drug design approaches were applied to identify chalcones with antiplasmodial activity. Methodology: The virtual screening was performed as follows: structural standardization of in-house database of chalcones; identification of potential Plasmodium falciparum protein targets for the chalcones; homology modeling of the predicted P. falciparum targets; molecular docking studies; and in vitro experimental validation. Results: Using these models, we prioritized 16 chalcones with potential antiplasmodial activity, for further experimental evaluation. Among them, LabMol-86 and LabMol-87 showed potent in vitro antiplasmodial activity against P. falciparum, while LabMol-63 and LabMol-73 were potent inhibitors of Plasmodium berghei progression into mosquito stages. Conclusion: Our results encourage the exploration of chalcones in hit-to-lead optimization studies for tackling malaria.