Sar-Based Design of Protease Inhibitors Novel Scarfold

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 biological targets. In this study, active fragments from prenylated and quinolinyl chalcones with known antimalarial activities were hybridized through molecular hybridization. Four enzymes 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 using Chimera and Discovery Studio Visualizer 2017. Web-based softwares (Moftsoft, SwissADME, AdmetSAR 1 and 2) were employed in drug-likeness and ADMET prediction. Hybridization of the active fragments resulted to a novel scarfold including 126 novel prenylated-quinolinyl chalcones. 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 (-9.4 to -7.5 kcal/gmol-1). The selected compounds demonstrated good drug-likeness and ADMET properties. The compounds exhibited plausible pharmacokinetics and pharmacodynamics properties in conjunction to their promising antimalarial activities which ranked them as potential antimalarial agent.

Author(s): Babalola S Adewale* , Idris A Yunusa, Hamza N Asmau, Muhammad Y Hayatuddeen

Abstract | PDF

Share This Article