Author(s): Maryam Norouzbahari, Emine V. Burgaz, Tugba Ercetin, Amirhossein Fallah, Alireza Foroumadi, Loghman Firoozpour, Mustafa F. Sahin, Mustafa Gazi, Hayrettin O. Gulcan*.
Considering the limitations of current cholinesterase inhibitor drugs for the treatment of Alzheimer’s disease, there is ongoing research activities to find out alternative drug candidates. The aryl-spacer-N-benzyl pharmacophore model has been effectively utilized to design various types of cholinesterase inhibitor molecules, including donepezil. Within this research study, we have questioned the significance of the benzyl group within this pharmacophore employing the urolithin derivatives. Urolithins are benzo[c]chromene analogue metabolites of ellagitannins, abundantly found in pomegranate and berry fruits. Read out full article here: http://www.eurekaselect.com/159057
Journal: Letters in Drug Design & Discovery
Author(s): Gulhan Turan-Zitouni*, Weiam Hussein, Begum Nurpelin Saglik, Merve Baysal, Zafer Asim Kaplancikli
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.
Read more here: http://www.eurekaselect.com/153764/article