Sitokiren Malate

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.

As an alternative of antibiotic therapy against drug-resistance or even multi-drug-resistant bacteria, antimicrobial photodynamic therapy (aPDT) is a promising therapeutic approach for cutaneous/oral localized infections as well as an efficient protocol for disinfection of blood products. In this study, a series of BODIPY derivatives modified with multi-quaternary ammonium cations were designed and synthesized. Density functional theory (DFT) showed that the ΔE values of new compounds were significantly reduced compared to the reference compound BDP-1. All new compounds exhibited intense absorption at 650 nm with high molar extinction coefficients for deeper tissue penetration, and obvious singlet oxygen generation ability. They had remarkable photodynamic activity against Staphylococcus aureus, particularly compounds I₁ and II₁ with the lowest minimum inhibitory concentrations (MIC). In vitro aPDT experiments showed that compounds I₁ and II₁ could disrupt the integrity of bacterial cell membranes, causing the leakage of cytoplasmic contents, and eradicate the mature biofilms of S. aureus. Notably, compound I₁ exhibited minimal toxicity toward human hepatocyte cell HL-7702. Since I₁ possessed significant photodynamic inactivation efficacy against S. aureus, obvious disruption capability to the formed biofilm, and minimal toxicity toward normal human cell, it could be suggested as a promising photosensitizer for aPDT and disinfection of blood products.