Synthesis and biological evaluations of 8-biaryl-2,2-dimethylbenzopyranamide derivatives against Alzheimer's disease and ischemic stroke.

Bioorg Chem

Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

Published: February 2024

Alzheimer's disease, the commonest cause of dementia, is a growing global health concern with huge implications for individuals and society. Stroke has still been a significant challenge in clinics for a long time, which is the second leading cause of death in the world, especially ischemic stroke. Both Alzheimer's disease and stroke are closely related to oxidative stress and HIF-1 signaling pathways in nerve cells. Herein, we describe our structure-based design, synthesis, and biological evaluation of a new class of 8-biaryl-2,2-dimethylbenzopyranamide derivatives as natural product derivatives. Our efforts have resulted in the discovery of highly potent neuroprotective agents, as exemplified by compound D13 as a HIF-1α inhibitor, which significant improvement in the behavior of Alzheimer's disease mice and shows great potential improvement of brain infarct volume in pMCAO model rats, improves the increase of blood-brain barrier permeability after cerebral ischemia in rats, neuroprotective effect, reduce the level of apoptotic cells in rats after cerebral ischemia, better than Edaravone.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2023.107064DOI Listing

Publication Analysis

Top Keywords

alzheimer's disease
16
synthesis biological
8
8-biaryl-22-dimethylbenzopyranamide derivatives
8
ischemic stroke
8
stroke alzheimer's
8
cerebral ischemia
8
biological evaluations
4
evaluations 8-biaryl-22-dimethylbenzopyranamide
4
alzheimer's
4
derivatives alzheimer's
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!