ABSTRACT
Multi-target-directed ligands (MTDLs) offer new hope for the treatment of multifactorial complex diseases such as Alzheimer's Disease (AD). Herein, we present compounds aimed at targeting the NMDA and the P2X7 receptors, which embody a different approach to AD therapy. On one hand, we are seeking to delay neurodegeneration targeting the glutamatergic NMDA receptors; on the other hand, we also aim to reduce neuroinflammation, targeting P2X7 receptors. Although the NMDA receptor is a widely recognized therapeutic target in treating AD, the P2X7 receptor remains largely unexplored for this purpose; therefore, the dual inhibitor presented herein-which is open to further optimization-represents the first member of a new class of MTDLs.
Subject(s)
Purinergic P2X Receptor Antagonists/chemistry , Purinergic P2X Receptor Antagonists/pharmacology , Receptors, Purinergic P2X/chemistry , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Cell Line, Tumor , Chemistry Techniques, Synthetic , Dose-Response Relationship, Drug , Drug Design , Drug Discovery , Humans , Inhibitory Concentration 50 , Ligands , Molecular Structure , Purinergic P2X Receptor Antagonists/chemical synthesis , Receptors, Purinergic P2X/metabolismABSTRACT
Sigma receptor (σR) ligands have proven to be useful as cancer diagnostics and anticancer therapeutics and their ligands have been developed as molecular probes in oncology. Moreover, various σR ligands generate cancer cell death in vitro and in vivo. These σR ligands have exhibited promising results against numerous human and rodent cancers and are investigated under preclinical and clinical study trials, indicating a new category of drugs in cancer therapy.
