Peptidomimetics based on natural cinnamic acid scaffold: Synthesis, bio-evaluation and structure-activity...

A total of twenty-one peptidomimetics based on cinnamic acid scaffold were synthesized through structure-activity relationship driven (SAR-driven) optimization of natural molecule (CSDK450160). Systematic bio-evaluation against twelve phytopathogenic fungi for these compounds revealed structure-dependent antifungal specificity, with cinnamic acid-peptide conjugates demonstrating pronounced inhibitory efficacy against Botrytis cinerea and Sclerotinia sclerotiorum. In planta antifungal assays showed that compound I-1 exhibited superior inhibitory potency against S. sclerotiorum. Scanning electron microscopy (SEM) analysis confirmed significant morphological disruption of S. sclerotiorum hyphae by I-1, including mycelial collapse and septation defects, effectively arresting mycelial proliferation. The mechanism of interaction between compound I-1 and potential target protein was described by integrating molecular docking technology and quantum chemistry theory. The theoretical results show that compound I-1 exhibits unique spatial structure specificity and achieves accurate recognition and highly selective binding with target proteins through π-π stacking.