Computational analysis of novel drugs designed for use as acetylcholinesterase inhibitors and histamine H 3 receptor antagonists for Alzheimer's disease by docking, scoring and de novo evolution

Po Yuan Chen, Ching Tsan Tsai, Che Yen Ou, Wei Tse Hsu, Mien De Jhuo, Chieh Hsi Wu, Tzu Ching Shih, Tzu Hurng Cheng, Jing Gung Chung

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 H 3 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 H 3 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.

Original languageEnglish
Pages (from-to)1043-1048
Number of pages6
JournalMolecular Medicine Reports
Volume5
Issue number4
DOIs
Publication statusPublished - Apr 2012
Externally publishedYes

Fingerprint

Cholinesterase Inhibitors
Histamine
Alzheimer Disease
Pharmaceutical Preparations
Acetylcholine
Monoamine Oxidase Inhibitors
N-Methylaspartate
Chelating Agents
Blood-Brain Barrier
Adsorption
Dementia
Anti-Inflammatory Agents
Theoretical Models
Antioxidants
Metals
Research Personnel
Metabolism
Toxicity
Transmitters
Research

Keywords

  • Acetylcholinesterase inhibitors
  • Alzheimer's disease
  • Histamine H receptor antagonists

ASJC Scopus subject areas

  • Biochemistry
  • Cancer Research
  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Oncology

Cite this

Computational analysis of novel drugs designed for use as acetylcholinesterase inhibitors and histamine H 3 receptor antagonists for Alzheimer's disease by docking, scoring and de novo evolution. / Chen, Po Yuan; Tsai, Ching Tsan; Ou, Che Yen; Hsu, Wei Tse; Jhuo, Mien De; Wu, Chieh Hsi; Shih, Tzu Ching; Cheng, Tzu Hurng; Chung, Jing Gung.

In: Molecular Medicine Reports, Vol. 5, No. 4, 04.2012, p. 1043-1048.

Research output: Contribution to journalArticle

Chen, Po Yuan ; Tsai, Ching Tsan ; Ou, Che Yen ; Hsu, Wei Tse ; Jhuo, Mien De ; Wu, Chieh Hsi ; Shih, Tzu Ching ; Cheng, Tzu Hurng ; Chung, Jing Gung. / Computational analysis of novel drugs designed for use as acetylcholinesterase inhibitors and histamine H 3 receptor antagonists for Alzheimer's disease by docking, scoring and de novo evolution. In: Molecular Medicine Reports. 2012 ; Vol. 5, No. 4. pp. 1043-1048.
@article{3c4f17d40d5c455c80c7c48679727829,
title = "Computational analysis of novel drugs designed for use as acetylcholinesterase inhibitors and histamine H 3 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 H 3 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 H 3 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.",
keywords = "Acetylcholinesterase inhibitors, Alzheimer's disease, Histamine H receptor antagonists",
author = "Chen, {Po Yuan} and Tsai, {Ching Tsan} and Ou, {Che Yen} and Hsu, {Wei Tse} and Jhuo, {Mien De} and Wu, {Chieh Hsi} and Shih, {Tzu Ching} and Cheng, {Tzu Hurng} and Chung, {Jing Gung}",
year = "2012",
month = "4",
doi = "10.3892/mmr.2012.757",
language = "English",
volume = "5",
pages = "1043--1048",
journal = "Molecular Medicine Reports",
issn = "1791-2997",
publisher = "Spandidos Publications",
number = "4",

}

TY - JOUR

T1 - Computational analysis of novel drugs designed for use as acetylcholinesterase inhibitors and histamine H 3 receptor antagonists for Alzheimer's disease by docking, scoring and de novo evolution

AU - Chen, Po Yuan

AU - Tsai, Ching Tsan

AU - Ou, Che Yen

AU - Hsu, Wei Tse

AU - Jhuo, Mien De

AU - Wu, Chieh Hsi

AU - Shih, Tzu Ching

AU - Cheng, Tzu Hurng

AU - Chung, Jing Gung

PY - 2012/4

Y1 - 2012/4

N2 - 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 H 3 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 H 3 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.

AB - 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 H 3 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 H 3 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.

KW - Acetylcholinesterase inhibitors

KW - Alzheimer's disease

KW - Histamine H receptor antagonists

UR - http://www.scopus.com/inward/record.url?scp=84863291864&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863291864&partnerID=8YFLogxK

U2 - 10.3892/mmr.2012.757

DO - 10.3892/mmr.2012.757

M3 - Article

C2 - 22267207

AN - SCOPUS:84863291864

VL - 5

SP - 1043

EP - 1048

JO - Molecular Medicine Reports

JF - Molecular Medicine Reports

SN - 1791-2997

IS - 4

ER -