Structural biology of plant-derived antibacterials: opportunities for rational lead optimization.

Structural biology has proven to be a pivotal tool in early-stage drug discovery, particularly in the lead optimization phase. Structure-activity relationship approaches have enabled the successful modification of plant-derived natural products into approved therapeutic agents. Despite the well-documented antibacterial potential of many phytochemicals, the number of plant-derived antibacterial drugs reaching clinical development remains limited. We highlight key case studies involving crystal structures of bacterial targets complexed with plant-derived natural products, elucidating their binding modes and mechanisms of action. We discuss the current challenges and opportunities for medicinal chemists pursuing rational lead optimization in the development of antibacterial drugs.