Sulfur-Containing Natural Products as Promising Cardiotonic and Anti-Ischemic Agents: Implications for Neuroprotection and Dementia Therapy
Abstract:
Sulfur-containing (SC) natural hydrocarbons represent a structurally diverse class of metabolites widely distributed in plant materials, foods, petroleum, crude oils, and fossil fuels. From a total of approximately 600 analyzed com pounds, 35 sulfur-containing metabolites were identified and selected for further investigation. In this study, these 35 SC metabolites were evaluated to assess their potential as cardiotonic and anti-ischemic agents using predictive biological activity modeling. The results revealed that compounds 1–14 exhibit strong cardiotonic activity (Pa up to 0.996), particularly among flexible, mono-sulfur macrocyclic and terpene-like structures. In contrast, compounds 15–35 demonstrated significant anti-ischemic (cerebral) activity (Pa up to 0.935), with simpler monosulfide and moderately flexible cyclic systems showing the highest potency. Structure–activity relationship (SAR) analysis indi cated that sulfur incorporation is a key determinant of biological activity, influencing lipophilicity, redox behavior, and molecular interactions with biological targets. Flexible monosulfides favor cardiotonic and anti-ischemic ef fects, while increased structural rigidity and sulfur multiplicity shift activity toward antiarrhythmic, neuroprotective, and cerebrovascular functions. Many compounds also exhibited multi-target pharmacological profiles, including antineoplastic, anti-inflammatory, antidepressant, and neurodegenerative disease-related activities. Mechanistical ly, the observed effects may be attributed to membrane interaction, modulation of oxidative stress, ion channel regulation, and interaction with protein thiol groups, supporting both cardiovascular and central nervous system (CNS) activity. Notably, several compounds showed predicted relevance to dementia and ischemic neurodegenera tion, suggesting their potential as multifunctional therapeutic agents. Overall, this study highlights sulfur-containing hydrocarbons as promising scaffolds for the development of novel cardiotonic, anti-ischemic, and neuroprotective drugs, and provides a foundation for future experimental validation and rational drug design.
