Title:Fighting Against Alzheimer's Disease: Synthesis of New Pyrazoline and Benzothiazole Derivatives as New Acetylcholinesterase and MAO Inhibitors
Volume: 15
Issue: 4
Author(s): Gulhan Turan-Zitouni*, Weiam Hussein, Begum Nurpelin Saglik, Merve Baysal and Zafer Asim Kaplancikli
Affiliation:
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskisehir,Turkey
Keywords:
Thiophene, 3-phenyl-2-pyrazoline, benzothiazole, acetylcholinesterase, Monoamine oxidase (MAO), MAO inhibitors,
Alzheimer's disease, molecular docking.
Abstract: Background: Alzheimer's Disease (AD) is a complicated neurodegenerative disorder
with a multifaceted pathogenesis.AD, characterized by gradual memory loss, falling in language
ability and other cognitive deterioration, and has been a prominent risk to ageing population. This
means that there is an urgent need to find new lead compounds for controlling and fighting against
(AD). In this way, a new thiophene-2-pyrazoline derivatives (A1-A5) and benzothiazole derivatives
(A6-A13) have been synthesized to give beneficial compounds to controlling and battling against
(AD).
Results: Compounds A5 and A13 showed the most remarkable activity with an 18.53 µM and 15.26
µM IC50 values against AChE enzyme. In like manner, compound A4 was active with a 20.34 µM
IC50 value against MAO-A. These active compounds are in fact non-toxic making them very attractive
for additional future studies. Enzyme kinetic was analyzed and the Lineweaver-Burk plot reveals
that compound A13 was typically mixed AChE inhibitors, which showed significant similarity
to donepezil. In addition, the best docking pose was done by analyzing the docking pattern of the
most active compound A13 which was very compatible with the gorge and in interaction with both
CAS and PAS.
Conclusion: The synthesis of new thiophene-2-pyrazoline and benzothiazole derivatives targeting
AChE/(MAO-A)/(MAO-B) enzymes was described. The selection of enzyme-kinetic analysis, molecular
docking and toxicity test was led to good understanding to the therapeutic potential for the
active derivatives. Therefore, these compounds may be accepted as promising leads for future research
efforts in fighting against AD.