Medicinal Chemistry of Khellin and Its Synthetic Derivatives: Progress and Future Potential in Drug Discovery

Abstract Khellin (1) is a natural furanocoumarin found in Ammi visnaga majus, renowned for its abundance of biological activities in various physiological conditions, including tumors, bacterial infections, inflammation, viral fibrosis, obesity, respiratory disease, and diabetes. Based on extensive site‐selective chemical modifications of 1 , various new chemical entities (NCEs) with enhanced bioavailability, potency, pharmacokinetics, and druggability have been developed over the years. Furthermore, the mechanisms of action at the molecular and cellular level have been thoroughly investigated in conjunction with preclinical studies. In this article, we present the medicinal chemistry of 1 and its derivatives in diverse drug discovery efforts covering the period from 2015 to the present. We have also elucidated the future perspectives, challenges, and limitations. We posit that this review will elucidate areas where 1 can be more beneficial in identifying hits and leads in drug discovery and enhance knowledge regarding its therapeutic applications.