Analysis of multi-target directed novel non-peptidic chalcone scaffold as potential malaria plasmodium proteases inhibitors

Malaria remain an epidermic infectious disease that is ravaging the world most especially sub-Sahara Africa. Due to the prevalence of Plasmodium parasites that are resistant to first-line antimalarial drugs, it is urgently necessary to create new scaffolds and find strategies to overcome drug resistance. Chalcones are well-known, uncomplicated analogs that may be easily produced using a variety of techniques and are widely present in natural products. Utilizing in silico tools, we developed new antimalarial agents from active synthetic and natural product fragments, and then we assessed their pharmacokinetics and pharmacodynamic profiles as therapeutic molecules against the biological targets of the parasite that causes the deadly type of malaria. In this research, active fragments from prenylated and quinolinyl chalcones with known antimalarial characteristics were combined via molecular hybridization. Four enzymes that have been implicated to the spread of malaria are used as the biological targets in the docking simulation for the ligands (prenylated-quinolinyl chalcone hybrids). Receptor-ligand complexes were viewed using Discovery Studio Visualizer 2017 and Chimera. Web-based tools (Moftsoft, SwissADME, Admetlab, and AdmetSAR 1 and 2) were utilized for drug-likeness and ADME prediction. The hybridized active segments created a brand-new scaffold with 169 new prenylated-quinolinyl chalcones. Post-docking studies found significant interactions between the drugs and the used targets. At least 25 of the compounds exhibit high affinities for the targets (-9.4 to -7.5 kcal/mol-1). The selected compounds had interesting ADME and drug-like properties. The compounds were qualified as possible antimalarial drugs due to their realistic pharmacokinetic and pharmacodynamic characteristics as well as their prospective antimalarial activity.