الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 225 |  |  |
| | | from | 225 | | |
Abstract
Background: The present study deals with synthesize new multi-target molecules against the multi factorial Alzheimer’s disease the choline esterase inhibitor core, tacrine, was incorporated into chromene moiety to produce modified tacrine-chromene hybrids. The tacrine was chosen to inhibit the ChE, and the chromene scaffold was used for BACE-1 and MAO-B inhibition. Besides, due to the aromatic character of the tacrine-chromene, it might have potential interaction with the PAS of AChE and have Aβ aggregation inhibition activity. Furthermore, the calcium channel blockade core (4-H-Pyran) was incorporated into tacrine-derived moiety and resulted in pyranotacrine derivatives.Methods: includes the synthetic procedures followed to obtain the target compounds, and biological screening against AChE, BuChE, BACE-1, MAO-B and Aβ inhibitory activity. Calcium channel blockade capacity, antioxidant activities, cytotoxicity, ability to chelate metals and molecular docking study were also performed. Results: Compounds 64c, 64d and 72c demonstrated superior activity against AChE, BuChE, and Aβ. Compounds 64c and 64d had inhibitory activity against BACE-1and MAO-B, while compound 72c was proved to be potent Ca+2 Channel blockade. They also had antioxidant activities and showed satisfactory metal-chelating. Furthermore, they showed acceptable relative safety upon normal cells SH-SY5Y and HepG2 and BBB penetrating activity.Conclusion: we can shed light on the significance of the chromene-tacrine and pyranotacrine derivatives in designing AD agents. Compounds 64c, 64d and 72c were proved to be multi-functional agents for AD and These multifunctional properties highlight that they can serve as promising candidates for further development of multi-functional drugs against AD