Natural and Synthetic Capsaicin Analogues: A Comprehensive Review of Biological Effects and Synthetic Pathways

Capsaicin analogs, whether sourced from natural origins or synthesized de novo, have garnered significant attention across diverse scientific disciplines. This comprehensive investigation explores the expansive domain of medicinal chemistry and pharmacology, focusing on capsaicin and its analogs. Notably, these analogs exhibit a wideranging pharmacological spectrum, with a particular emphasis on their potent antitumor properties. Researchers frequently explore structural modifications, particularly in region C, consistently enhancing their pharmacological activities. A highlighted finding is that analogs with alterations in both regions A and C manifest a diverse array of effects, spanning from anti-obesity to protection against ischemia. They also demonstrate anti- Alzheimer's, anti-fibrotic, anti-inflammatory, anti-diabetic, antimalarial, and anti-epileptic properties. This underscores the potential of structural adaptations in these regions, expanding the therapeutic applications of capsaicin-like compounds. Additionally, manipulations in regions B and C result in compounds that possess antioxidant and anti-obesity properties, providing valuable insights for the development of novel compounds. The therapeutic potential of capsaicin analogs opens innovative avenues for drug design and development, promising to address a broad spectrum of diseases and enhance global quality of life. Moreover, this article meticulously examines various synthetic methodologies for synthesizing capsaicin analogs, complementing the main review. These methodologies distinguish themselves through their simplicity, mild reaction conditions, and reliance on readily available commercial reagents. The accessible synthesis pathways enable researchers from diverse backgrounds to explore these compounds, fostering investigations and potential therapeutic applications.