To screen the active antimalarial novel artemisinin derivatives, a QSAR modeling 
approach was used. QSAR model showed high correlation (r(2)= 0.83 and rCV(2)= 
0.81) and indicated that Connectivity Index (order 1, standard), Connectivity 
Index (order 2, standard), Dipole Moment (debye), Dipole Vector X (debye) and 
LUMO Energy (eV) well correlate with activity. High binding likeness on 
antimalarial target plasmepsin was detected through molecular docking. Active 
artemisinin derivatives showed significant activity and indicated compliance 
with standard parameters of oral bioavailability and ADMET. The active 
artemisinin derivatives namely, β-Artecyclopropylmether HMCP (A3), β- 
Artepipernoylether (PIP-1) (A4) and 9-(β-Dihydroartemisinoxy)methyl anthracene 
(A5) were semi-synthesized and characterized based on its (1)H and (13)C NMR 
spectroscopic data and later activity tested in vivo on mice infected with 
multidrug resistant strain of P. yoelii nigeriensis. Predicted results were 
successfully validated by in vivo experiments.