Analysis of Multi Target Directed Non Peptidic Compounds as Potential Malaria Inhibitors against Plasmodium Proteases through Structure Activity Relationship and Virtual Screening Workflow

Purpose: To design new antimalarial agents from both active synthetic and natural products fragments using in-silico software to determine their pharmacokinetics and pharmacodynamics profiles as therapeutic molecules against the deadly malaria causing parasite P. falciparum biological targets. Methods: In this study, active fragments from crenelated and quinolinyl chaconnes with known antimalarial activities were hybridized through molecular hybridization. Four P. falciparum enzymes including plasmepsin II, Falcipain 2, Falcipain 3, and SUB1 which have been reported to be involved in malaria transmission are used as the biological targets for the ligands (prenylated-quinolinyl chalcones hybrids) during docking simulation. Receptor-ligand complexes were viewed. Web-based softwares (Moftsoft, SwissADME, AdmetSAR 1 and 2) were employed in druglikeness and ADMET prediction. Results: Hybridization of the active fragments resulted to a novel scaffold including 126 novel prenylated-quinolinyl chaconnes. Post-docking analysis revealed strong interactions of the compounds with the targets used. At least 25 of the compounds have high affinities for the targets. The selected compounds demonstrated good drug-likeness and ADMET properties. Conclusion: The compounds exhibited plausible pharmacokinetics and

Author(s): Babalola S Adewale

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