Skip to main content

Molecular Interaction of the Antineoplastic Drug, Methotrexate with Human Brain Acetylcholinesterase: A Docking Study

Buy Article:

$63.00 plus tax (Refund Policy)

Abstract:

This study describes molecular interactions between human brain acetylcholinesterase (AChE) and the well known anti-neoplastic drug, methotrexate (MTX) and its comparison to ‘AChE-cyclophosphamide (CP) interactions’ that we reported previously. Docking between MTX and AChE was performed using ‘Autodock4.2’. Hydrophobic interactions and hydrogen bonds both play an equally important role in the correct positioning of MTX within the ‘acyl pocket’ as well as ‘catalytic site’ of AChE to permit docking. However, docking of CP to AChE is largely dominated by hydrophobic interactions. Such information may aid in the design of versatile AChE-inhibitors, and is expected to aid in safe clinical use of MTX. Scope still remains in the determination of the three-dimensional structure of AChE-MTX complex by X-ray crystallography to validate the described data. The current computational study supports our previous experimental study which concluded a mixed inhibition model for AChE-inhibition by MTX. Furthermore, the present report confirms that MTX is a more efficient inhibitor of human brain AChE compared to CP with reference to Ki and ΔG values.





Keywords: AChE; CTX-M-15; Cefotaxime; Cephalosporin; Cyclophosphamide; Desolvation; Docking; Enzyme-Inhibition; Galantamine; Human Brain Acetylcholinestrase; MTX; Methotrexate

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/187152712800269669

Affiliations: King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia.

Publication date: March 1, 2012

More about this publication?
  • CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
ben/cnsnddt/2012/00000011/00000002/art00007
dcterms_title,dcterms_description,pub_keyword
6
5
20
40
5

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more