Scaffold Hopping in Agricultural Antibacterials: Research Progress and Prospects

Plant bacterial diseases cause substantial economic losses in agricultural production annually. Conventional agricultural antibacterial agents, including copper-based formulations and antibiotics, exhibit notable limitations, underscoring the urgency for developing novel agricultural antibacterial agents. Scaffold hopping is a viable strategy to address key challenges in antibacterial agent development (such as insufficient bioactivity, intellectual property barriers, high structural complexity of lead compounds, poor metabolic stability, and adverse toxicological profiles), thereby enabling the generation of isomeric functional molecules with comparable or enhanced properties. To facilitate the development of novel, high-efficiency, low-toxicity agricultural antibacterial agents, we systematically review the application of scaffold hopping in the development of antibacterial derivatives. Notably, scaffold hopping combined with structure-activity relationship (SAR) analyses can address the inherent limitations of developing novel antibacterials, expand the active molecule chemical space, and improve derivative development efficiency. We also summarized and prospectively discussed the application of scaffold hopping in antibacterial agent derivatives and their mechanisms. Scaffold hopping can offer valuable insights into the development of antibacterial derivatives and is of guiding significance for the research and development of novel antibacterial agrochemicals.