Journal of Clinical & Experimental Pharmacology

Terpenoids as promising therapeutic molecules against Alzheimerâ??s disease: Amyloid beta and acetylcholinesterase directed pharmacokinetic and molecular docking analyses

3^rd World Congress on Pharmacology

August 08-10, 2016 Birmingham, UK

Manika Awasthi, Arun K Upadhyay, Swati Singh, Veda P Pandey and Upendra N Dwivedi

University of Lucknow, India

Posters & Accepted Abstracts: Clin Exp Pharmacol

Abstract:

Alzheimer�??s disease (AD) is a progressive neurological disorder characterized by deterioration of cognitive functions and behavioral changes including dementia. Several attempts have been made to treat AD by combined drug therapy directed against acetylcholinesterase (AChE) and amyloid beta (Aβ) simultaneously for delaying the progression of the disease. However, the sideeffects due to long-term administration of these drugs have motivated attempts for development of a new generation of therapeutics based on natural compounds. In this regard, one hundred terpenoids having neuroprotective properties were analyzed for their inhibitory potential against AChE and Aβ through molecular docking approach. In view of the fact that ADMET analyses of potential therapeutic compounds is essential for ensuring the development of safer drugs, the selected terpenoids were further screened for their pharmacokinetic properties, among which only twenty five terpenoids were found to fulfill all the ADMET descriptors and drug likeness properties. A triterpene, nimbolide, was found to be the most potent and safe inhibitor for both AChE and Aβ among the selected terpenoids as well as those of commonly used drug and known inhibitor, namely galanthamine and curcumin, respectively. Molecular dynamics simulation analysis of AChE-nimbolide and Aβ-nimbolide complexes also validated the results of docking. These findings well corroborated with the traditional knowledge of use of neem tree (Azadirachta indica), the source of nimbolide, in the treatment of AD. Thus, the present work makes a foundation for further clinical investigations of nimbolide as a drug for AD.

Biography :

Email: manikaawasthi09@gmail.com