Designing 1,4-Dihydropyridines-Based Multitarget Therapeutics: Recent Advances and Future Directions.

BACKGROUND: 1,4-Dihydropyridines (1,4-DHPs) serve as versatile scaffolds in medicinal chemistry, exhibiting multitarget potential with anticancer, cardiovascular, antioxidant, antiinflammatory, antimicrobial, and analgesic effects. Structural modifications enhance their binding affinity, bioavailability, and selectivity. AIM: This review aims to explore the broad therapeutic potential of 1,4-DHPs by analyzing their biological activities and structure-activity relationships (SAR). Additionally, it seeks to provide medicinal chemists with insights into key structural modifications that can optimize their pharmacological efficacy. METHOD: A comprehensive literature search was conducted in PubMed, ScienceDirect, Elsevier, and Google Scholar, prioritizing peer-reviewed studies from the last decade. Inclusion criteria focused on pharmacological properties, SAR, and therapeutic potential of 1,4-DHPs, while nonpeer- reviewed or irrelevant studies were excluded. Data extraction analyzed SAR trends, emphasizing the impact of structural modifications on binding affinity, bioavailability, and biological activity. RESULTS: The review highlights that specific modifications in aromatic substituents, ester groups, and heterocyclic rings play a crucial role in enhancing the biological activity and selectivity of 1,4- DHPs. Their ability to modulate key enzymes and receptors contributes to their effectiveness as multitarget agents. Comparative SAR analysis provides evidence of the potential of 1,4-DHPs as next-generation therapeutics. CONCLUSION: 1,4-DHPs offer a promising framework for drug development, with the potential to address complex, multifactorial diseases. By understanding and optimizing SAR, medicinal chemists can design more selective and potent 1,4-DHP-based drugs. Future research should focus on refining these structural modifications to unlock their full therapeutic potential.