title: Computational analysis of novel drugs designed for use as acetylcholinesterase inhibitors and histamine H3 receptor antagonists for Alzheimer's disease by docking, scoring and de novo evolution.
abstract: Alzheimer's disease (AD) was first described by Alois Alzheimer in 1907. AD is the most prevalent dementia- related disease, affecting over 20 million individuals worldwide. Currently, however, only a handful of drugs are available and they are at best only able to offer some relief of symptoms. Acetylcholinesterase (AChE) inhibitors, antioxidants, metal chelators, monoamine oxidase inhibitors, anti-inflammatory drugs and NMDA inhibitors are usually used to attempt to cure this disease. AChE inhibitors are the most effective therapy for AD at present. Researchers have found that histamine H3 receptor antagonists decrease re-uptake of acetylcholine and the nervous transmitter substance acetylcholine increases. In this study, we designed compounds by using docking, de novo evolution and adsorption, distribution, metabolism, excretion and toxicity (ADMET) analysis to AChE inhibitors as well as histamine H3 receptor antagonists to forward drug research and investigate the potent compounds which can pass through the blood-brain barrier. The novel drugs may be useful for the treatment of AD, based on the results of this theoretical calculation study. We will subsequently examine them in future experiments.
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan, ROC.
authors.forename: Po-Yuan
authors.initials: PY
authors.lastname: Chen
authors.forename: Ching-Tsan
authors.initials: CT
authors.lastname: Tsai
authors.forename: Che-Yen
authors.initials: CY
authors.lastname: Ou
authors.forename: Wei-Tse
authors.initials: WT
authors.lastname: Hsu
authors.forename: Mien-De
authors.initials: MD
authors.lastname: Jhuo
authors.forename: Chieh-Hsi
authors.initials: CH
authors.lastname: Wu
authors.forename: Tzu-Ching
authors.initials: TC
authors.lastname: Shih
authors.forename: Tzu-Hurng
authors.initials: TH
authors.lastname: Cheng
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D001665:Binding Sites; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D019295:Computational Biology; D003198:Computer Simulation; D015195:Drug Design; D054828:Histamine H3 Antagonists / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D017434:Protein Structure, Tertiary; D018100:Receptors, Histamine H3 / Q000737:chemistry / Q000378:metabolism; D012984:Software
chemical_list: D002800:Cholinesterase Inhibitors; D054828:Histamine H3 Antagonists; D018100:Receptors, Histamine H3; D000110:Acetylcholinesterase