Progress in Synthetic Approaches and Pharmacological Applications of Melatonin and Its Derivatives: A Comprehensive Review

A neurohormone with strong central nervous system activity, melatonin plays a role in regulating circadian rhythms. It affects practically all tissues and organs and has a broad functional repertoire. It is primarily employed as a dietary supplement; melatonin aids in sleep regulation and the re-establishment of arousal cycles. Despite having very low toxicity, melatonin's tissue availability is constrained by pharmacokinetic problems such as poor oral bioavailability and a brief half-life. The synthesis and medicinal applications of melatonin and its derivatives are the main focus of this review study. Melatonin is considered as a beneficial agent suitable for safely treating and preventing various health conditions. This review covers synthesis approaches and pharmacological applications of melatonin and its derivatives published from the 1990s to 2024. The latest development in several studies involves the concurrent administration of melatonin with other drugs to enhance therapeutic effectiveness and mitigate adverse effects. Hybrid ligands, such as melatonin-tamoxifen and melatonin-tacrine derivatives are combined to give distinct effects. This review highlights the importance of continued research into melatonin and its derivatives, paving the way for developing novel and more potent therapeutic agents.