Natural bioactive compounds are valuable resources for drug discovery due to their diverse and unique structures. However, these compounds often lack optimal drug-like properties. Therefore, structural optimization is a crucial step in the drug development process. By employing medicinal chemistry principles, targeted molecular operations can be applied to natural products while considering their size and complexity. Various strategies, including structural fragmentation, elimination of redundant atoms or groups, and exploration of structure-activity relationships, are utilized. Furthermore, improvements in physicochemical properties, chemical and metabolic stability, biophysical properties, and pharmacokinetic properties are sought after. This article provides a concise analysis of the process of modifying a few marketed drugs as illustrative examples.
Keywords: drug discovery; medicinal chemistry; natural bioactive compounds; structure-activity relationships.