Marilia Nn Lima1, Bruno J Neves1,2, Gustavo C Cassiano3, Marcelo N Gomes1,4,5, Kaira Cp Tomaz3, Leticia T Ferreira3, Tatyana A Tavella3, Juliana Calit6, Daniel Y Bargieri6, Eugene N Muratov7,8, Fabio Tm Costa3, Carolina Horta Andrade1,3. 1. LabMol, Laboratory for Molecular Modeling & Drug Design, Faculty of Pharmacy, Federal University of Goiás, Rua 240, Qd. 87, Goiânia, GO 74605-170, Brazil. 2. Laboratory of Cheminformatics, University Center of Anápolis (UniEVANGÉLICA), Anápolis, GO 75083-515, Brazil. 3. Laboratory of Tropical Diseases, Prof. Dr. Luiz Jacintho da Silva, Department of Genetics, Evolution, Microbiology & Immunology, Institute of Biology, UNICAMP, Campinas, SP 13083-970, Brazil. 4. Metropolitan College of Anápolis, FAMA, Anápolis, GO 75064-780, Brazil. 5. InSiChem Drug Discovery, Anápolis, GO 75132-903, Brazil. 6. Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. 7. Laboratory for Molecular Modeling, Division of Chemical Biology & Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27955-7568, USA. 8. Department of Chemical Technology, Odessa National Polytechnic University, Odessa, 65000, Ukraine.
Abstract
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.
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.
Authors: Anna Gaulton; Louisa J Bellis; A Patricia Bento; Jon Chambers; Mark Davies; Anne Hersey; Yvonne Light; Shaun McGlinchey; David Michalovich; Bissan Al-Lazikani; John P Overington Journal: Nucleic Acids Res Date: 2011-09-23 Impact factor: 16.971
Authors: Marcelo N Gomes; Eugene N Muratov; Maristela Pereira; Josana C Peixoto; Lucimar P Rosseto; Pedro V L Cravo; Carolina H Andrade; Bruno J Neves Journal: Molecules Date: 2017-07-25 Impact factor: 4.411