J Appl Biomed 12:285-290, 2014 | DOI: 10.1016/j.jab.2014.01.010

Low molecular weight precursor applicable for Alzheimer disease drugs synthesis (AChE and BChE inhibition, BACE inhibition, antioxidant properties and in silico modulation)

Lucie Drtinova^a, Petr Dobes^b, Miroslav Pohanka^a,c,*

^a Faculty of Military Health Sciences, University of Defense, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic

^b Masaryk Memorial Cancer Institute in Brno, Zluty kopec 7, Brno, Czech Republic

^c Karel English College in Brno, Sujanovo namesti 356/1, 602 00 Brno, Czech Republic

Alzheimer disease (AD) is the most common cause of progressive dementia in the elderly population, with prevalence of 5% after 65 year of age and is increasing to about 30% in people over 85 year. AD is a neurodegenerative and incurable disease. Currently, three inhibitors of acetylcholinesterase (AChE), galantamine, donepezil and rivastigmine, and one inhibitor of N-methyl-d-aspartate (NMDA) receptor are available as drugs for amelioration of the disease. Demand to prepare drugs for the therapy providing at least relieve of symptoms remains. In this experiment, the ability of standards (donepezil, galantamine, huperzine A, tacrine and 7-methoxytacrine) and precursors used for synthesis of new AD drugs (l-tryptophan, pyridoxine B₆, tryptamine, acridine, chinoline, isochinoline, indole, pyridine and piperidine) to inhibit AChE, BChE and BACE or to have the antioxidant properties were determined. The results were compared using statistical expression of the relationship between the performed tests. In this experiment, IC₅₀ for every one method and every compound were found. Beside this, prediction of free energy in a link to ln(IC₅₀) was assessed using in silico tests. This article focuses on possibility to find the most suitable chemical precursors to be used in the next development of drugs for AD.

Keywords: Acetylcholinesterase; Alzheimer disease; Inhibition; Betasecretase; Neurodegeneration

Received: January 23, 2014; Revised: January 28, 2014; Accepted: January 30, 2014; Published: November 1, 2014  Show citation