Design,Synthesis,Molecular Docking,Molecular Dynamics and In Vivo Antimalarial Activity of New Dipeptide-Sulfonamides

摘要

A new series of novel dipeptide sulfonamide analogues were designed,synthesized,and screened for their in silico studies and in vivo antimalarial activities.The synthesized compounds(50 mg/Kg)showed significant activity against P.berghei(NK65)with % inhibition values in(5.9 to 64.7%)range in when compared with reference drug,artemisinin(66.7%)in a four day suppressive assay.The in silico studies predicted favorable binding affinity of compounds with target protein residues with high dock score against P.falciparum falcipain 2(FP-2)and falcipain 3(FP-3)proteins in comparison with the reference ligands.The synthesized compounds showed druggable properties,and the predicted(absorption,distribution,metabolism,excretion and toxicities(ADMET)properties were within the acceptable limits.Molecular dynamics simulation study of the most active compound,8e was performed in order to further validate the stability of the protein-ligand complex and the protein-ligand interactions.