title: QSAR and docking based semi-synthesis and in vivo evaluation of artemisinin derivatives for antimalarial activity.
abstract: 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.
authors: Dharmendra Kumar
authors: DK
authors: Yadav
authors: Sangeeta
authors: S
authors: Dhawan
authors: Akanksha
authors: A
authors: Chauhan
authors: Tabish
authors: T
authors: Qidwai
authors: Pooja
authors: P
authors: Sharma
authors: Rajendra Singh
authors: RS
authors: Bhakuni
authors: Om Prakash
authors: OP
authors: Dhawan
authors: Metabolic & Structural Biology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O.-CIMAP, Kukrail Picnic Spot Road, Lucknow-226015 (U.P.) India. f.khan@cimap.res.in.
authors: Feroz
authors: F
authors: Khan
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000378:metabolism* / Q000493:pharmacokinetics*; D037621:Artemisinins / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D001682:Biological Availability; D017076:Computer-Aided Design; D004195:Disease Models, Animal; D015195:Drug Design; D009682:Magnetic Resonance Spectroscopy; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D062105:Molecular Docking Simulation; D010967:Plasmodium yoelii / Q000187:drug effects; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship
chemical_list: C000595508:9-(beta-dihydroartemisinoxy)methylanthracene; D000962:Antimalarials; D037621:Artemisinins; D015800:Protozoan Proteins; C000595506:beta-artecyclopropylmether HMCP-1; C000595507:beta-artepipernoylether; C031327:artemisinin; D016282:Aspartic Acid Endopeptidases; C100637:plasmepsin II