Details

Autor(en) / Beteiligte

• Zhu, Gaofeng
• Bai, Ping
• Wang, Keren
• Mi, Jing
• Yang, Jing
• Hu, Jiaqi
• Ban, Yujuan
• Xu, Ran
• Chen, Rui
• Wang, Changning
• Tang, Lei
• Sang, Zhipei

Titel

Design, synthesis, and evaluation of novel O-alkyl ferulamide derivatives as multifunctional ligands for treating Alzheimer's disease

Ist Teil von

• Journal of enzyme inhibition and medicinal chemistry, 2022-12, Vol.37 (1), p.1375-1388

Ort / Verlag

England: Taylor & Francis

Erscheinungsjahr

2022

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Herein, a series of novel O-alkyl ferulamide derivatives were designed and synthesised through the multi-target-directed ligands (MTDLs) strategy. The biological activities in vitro showed that compounds 5a, 5d, 5e, 5f, and 5h indicated significantly selective MAO-B inhibitory potency (IC 50 = 0.32, 0.56, 0.54, 0.73, and 0.86 μM, respectively) and moderate antioxidant activity. Moreover, compounds 5a, 5d, 5e, 5f, and 5h showed potent anti-inflammatory properties, remarkable effects on self-induced Aβ 1-42 aggregation, and potent neuroprotective effect on Aβ 1-42 -induced PC12 cell injury. Furthermore, compounds 5a, 5d, 5e, 5f, and 5h presented good blood-brain barrier permeation in vitro and drug-like properties. More interesting, the PET/CT images with [ 11 C]5f demonstrated that [ 11 C]5f could penetrate the BBB with a high brain uptake and exhibited good brain clearance kinetic property. Therefore, compound 5f would be a promising multi-functional agent for the treatment of AD.