New Hybrid Compounds Incorporating Natural Products as Multifunctional Agents against Alzheimer's Disease

• Published in: Pharmaceutics Vol. 15; no. 10; p. 2369
• Main Authors: Ciccone, Lidia, Camodeca, Caterina, Tonali, Nicolò, Barlettani, Lucia, Rossello, Armando, Fruchart Gaillard, Carole, Kaffy, Julia, Petrarolo, Giovanni, La Motta, Concettina, Nencetti, Susanna, Orlandini, Elisabetta
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.09.2023; MDPI
• Subjects: Acids; Advertising executives; Aggregates; Alzheimer's disease; Amino acids; amyloid β (Aβ); antioxidant; Brain; chelating agents; Chromatography; Disease; Drug therapy; Life Sciences; Medical research; Natural products; neuroprotection; Physiology; Proteins; Toxicity; Transthyretin; TTR; Germany; United States > US; positive cross-interaction; antioxidant; TTR; neuroprotection; Transthyretin; chelating agents; amyloid β (Aβ); Aβ1-40
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics15102369

A series of new hybrid derivatives - , - , - , - , - , inspired by nature, were synthesized and studied as multifunctional agents for the treatment of Alzheimer's disease (AD). These compounds were designed to merge together the trifluoromethyl benzyloxyaminic bioactive moiety, previously identified, with different acids available in nature. The ability of the synthesized compounds to chelate biometals, such as Cu , Zn and Fe , was studied by UV-Vis spectrometer, and through a preliminary screening their antioxidant activity was evaluated by DPPH. Then, selected compounds were tested by in vitro ABTS free radical method and ex vivo rat brain TBARS assay. Compounds - , combining the strongest antioxidant and biometal chelators activities, were studied for their ability to contrast Aβ fibrillization process. Finally, starting from the promising profile obtained for compound , we evaluated if it could be able to induce a positive cross-interaction between transthyretin (TTR) and Aβ in presence and in absence of Cu .