Ciccone Lidia, Camodeca Caterina, Tonali Nicolò, Barlettani Lucia, Rossello Armando, Fruchart Gaillard Carole, Kaffy Julia, Petrarolo Giovanni, La Motta Concettina, Nencetti Susanna, Orlandini Elisabetta
Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy.
CNRS, BioCIS, Bâtiment Henri Moissan, Université Paris-Saclay, 17 Av. des Sciences, 91400 Orsay, France.
Pharmaceutics. 2023 Sep 22;15(10):2369. 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.
受自然启发，合成了一系列新型杂化衍生物——、——、——、——、——，并作为治疗阿尔茨海默病（AD）的多功能药物进行了研究。这些化合物的设计目的是将先前鉴定出的三氟甲基苄氧基胺生物活性部分与自然界中可得的不同酸结合在一起。通过紫外可见光谱仪研究了合成化合物螯合生物金属（如铜、锌和铁）的能力，并通过初步筛选，用DPPH评估了它们的抗氧化活性。然后，通过体外ABTS自由基法和离体大鼠脑硫代巴比妥酸反应物（TBARS）测定法对选定的化合物进行了测试。结合了最强抗氧化剂和生物金属螯合剂活性的化合物——，研究了它们对抗Aβ纤维化过程的能力。最后，从化合物——获得的有前景的特征出发，我们评估了它在有铜和无铜的情况下是否能够诱导转甲状腺素蛋白（TTR）和Aβ之间产生正向交叉相互作用。
