Design, synthesis, and evaluation of novel O -alkyl ferulamide derivatives as multifunctional ligands for treating Alzheimer’s disease
Year: 2022
Type: article
Abstract: 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 (IC50 = 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 Aβ1-42 aggregation, and potent neuroprotective effect on Aβ1-42-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 [11C]5f demonstrated that [11C]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.
Authors: Gaofeng Zhu, Ping Bai, Keren Wang, Jing Mi, Jing Yang, Jiaqi Hu, Yujuan Ban, Ran Xu, Rui Chen, Changning Wang, Lei Tang, Zhipei Sang
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,306
Funders: Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents, Guizhou Science and Technology Corporation Platform Talents Fund, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, National Joint Engineering Research Center for Abrasion Control and Molding of Metal Materials
Awards: G3624286324, G6027961700, G742641344
OpenAlex ID: W4280531376