title: Haloperidol inhibits Memapsin 2: innovation by docking simulation and in vitro assay.
abstract: A number of drugs exhibit unexpected pharmacological effects related to their ability to bind more than one receptor in humans. Haloperidol a typical antipsychotic drug appeared in several reports to be used in schizophrenia patients in which the significant of Alzheimer's disease has been reduced. The etiology of the disease is characterized by aggregates of amyloid plaques, largely composed of amyloid-β peptide formed from the amyloid precursor protein cleaved by Memapsin 2. To investigate if haloperidol can bind to Memapsin 2 active site, an initial molecular docking was performed as a preliminary in-silico screening test followed by in vitro enzyme inhibition assay. Haloperidol was found to fit readily in Memapsin binding site with IC(50)value 250mM. Haloperidol can be considered as important lead or important target can be modified for more inhibitory activity, with the intention of protection or treatment for Alzheimer's disease.
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Applied Science University, Amman, Jordan.
authors.forename: Afaf Hasan
authors.initials: AH
authors.lastname: Al-Nadaf
authors.affiliation: Drug Discovery Unit, Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Jordan, Amman, Jordan.
authors.forename: Mutasem Omar
authors.initials: MO
authors.lastname: Taha
authors.affiliation: Department of Medical Support, Al-Balqa Applied University, Al-Karak University College, Al-Karak, Jordan.
authors.forename: Hammad Khalifeh
authors.initials: HK
authors.lastname: Aldal'in
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D001665:Binding Sites; D015195:Drug Design; D006220:Haloperidol / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D006220:Haloperidol