Original Articles
Hanaa H. Ahmed, Gamal A. Elmeg
Abstract
Alzheimer's disease (AD) is a multi-factorial disease, thus the successful treatment will likely require the development of hybrid structures that target multiple systems. This was achieved through combination of two molecules to obtain new drug candidate. Although curcumin was believed to have high biological activity, it has drawbacks that affect its biological activity. Modification of curcumin moiety by synthesizing new derivatives has a great attention to improve its bioavailability. Moreover, the addition of heterocyclic rings to steroids molecules often leads to a change of their biological activity and appearance of new interesting pharmacological properties. Based on these evidences, our goal was to synthesize new hybrid drugs and to elucidate the efficacy of these novel synthesized compounds in the recession of AD induced in adult female albino rats. This goal was achieved by reacting curcumin with different reagent to get new heterocyclic derivatives. Besides that, steroid moiety was also modified by submitting it to react it with various reagent to form new hybrid molecules. The resulting compounds 7a and 13c were tested as anti-Alzheimer's disease in vivo through targeting multiple pathways implicated in the pathogenesis of AD. The results showed the anti-Alzheimer’s disease of the two compounds with different degrees depending on their structure where compound 13c showed strongest activity than compound7a. In conclusion, the addition or fusion of heterocyclic rings in curcumin or steroid molecule could improve their biological activity in regression of AD in the experimental model. The biological study provides clear evidence for the anti-Alzheimer's disease potency of the newly synthesized derivatives through their anti-cholinesterase activity, antioxidant property and antiapoptotic potential.