Neuroprotective Properties and Molecular Mechanisms of Action of 4H-Pyran-Based Acids.

Abstract

The development of effective neuroprotective agents remains one of the most urgent and complex challenges in modern medical and biological research, given the increasing prevalence of neurodegenerative diseases and the limited efficacy of existing therapeutic options. In recent years, compounds belonging to the 4H-pyran chemical class have attracted significant attention due to their pronounced antioxidant, anti-inflammatory, and cytoprotective properties. These molecules exhibit structural versatility, enabling modulation of multiple molecular targets involved in neuronal survival, redox homeostasis, and mitochondrial function. This review provides a comprehensive analysis of the pharmacological activity and molecular mechanisms of action of five 4H-pyran-based compounds-maltol, kojic acid, chelidonic acid, comenic acid, and meconic acid. Special attention is paid to their effects on signaling pathways that play a central role in maintaining neuronal integrity and resistance to stress factors. In particular, the review examines how these compounds regulate key intracellular cascades such as nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)/antioxidant response element (ARE), Nrf2/PTEN-induced putative kinase 1 (PINK1)/Parkin, nuclear factor-kappa B (NF-κB), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), which are critically involved in controlling oxidative stress, mitochondrial autophagy, inflammation, and neuronal plasticity. The integrated evaluation of these mechanisms demonstrates that 4H-pyran-based acids can act as multitarget neuroprotective agents capable of influencing both primary metabolic processes and secondary signaling responses to neurotoxic stimuli. Their pleiotropic action highlights the promise of these compounds as molecular scaffolds for the development of novel drugs aimed at preventing or delaying the progression of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases.