Mingoia Marina, Conte Carmela, Di Rienzo Annalisa, Dimmito Marilisa Pia, Marinucci Lorella, Magi Gloria, Turkez Hasan, Cufaro Maria Concetta, Del Boccio Piero, Di Stefano Antonio, Cacciatore Ivana
Department of Biomedical Sciences and Public Health, Medical School, Polytechnic University of Marche, 60121 Ancona, Italy.
Department of Pharmaceutical Sciences, University of Perugia, Via Fabretti, 48, 06123 Perugia, Italy.
Pharmaceuticals (Basel). 2022 Feb 15;15(2):228. doi: 10.3390/ph15020228.
The main antimicrobial resistance (AMR) nosocomial strains (ESKAPE pathogens such as , , , , , and spp.) are the most widespread bacteria in cutaneous infections. In this work we report the synthesis, in silico skin permeability prediction, antimicrobial, antibiofilm, and wound healing properties of novel cinnamic acid-based antimicrobials () as novel antibacterial drugs for the treatment of ESKAPE-related skin infections. Antimicrobial and wound healing scratch assays were performed to evaluate the antibacterial properties of . In silico skin permeability capabilities of were evaluated using Swiss-ADME online database. Cytotoxicity assays were performed on keratinocytes and fibroblasts. , bearing a catechol group on the aromatic ring of the cinnamic portion of the molecule, possesses a significant antibacterial activity against (MIC range 16-64 mg/L) and contrasts the biofilm-mediated infection at low concentrations. Wound healing assays showed that wound closure in 48 h was observed in -treated keratinocytes with a better healing pattern at all the used concentrations (0.1, 1.0, and 10 µM). A potential good skin permeation for , that could guarantee its effectiveness at the target site, was also observed. Cytotoxicity studies revealed that may be a safe compound for topical use. Taking together all these data confirm that could represent a safe wound-healing topical agent for the treatment of skin wound infections caused by two of main Gram-positive bacteria belonging to ESKAPE microorganisms.
主要的抗菌耐药（AMR）医院菌株（如屎肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和阴沟肠杆菌等ESKAPE病原体）是皮肤感染中最常见的细菌。在这项工作中，我们报告了新型肉桂酸类抗菌剂（）作为治疗与ESKAPE相关皮肤感染的新型抗菌药物的合成、计算机模拟皮肤渗透性预测、抗菌、抗生物膜和伤口愈合特性。进行了抗菌和伤口愈合划痕试验以评估的抗菌性能。使用瑞士ADME在线数据库评估了的计算机模拟皮肤渗透能力。对角质形成细胞和成纤维细胞进行了细胞毒性试验。在分子肉桂部分的芳香环上带有儿茶酚基团的，对具有显著的抗菌活性（MIC范围为16 - 64 mg/L），并在低浓度下对抗生物膜介导的感染。伤口愈合试验表明，在所有使用浓度（0.1、1.0和10 µM）下，用处理的角质形成细胞在48小时内观察到伤口闭合，且愈合模式更好。还观察到具有潜在良好的皮肤渗透性，这可以保证其在靶部位的有效性。细胞毒性研究表明，可能是一种安全的局部用药化合物。综合所有这些数据证实，可能是一种安全的伤口愈合局部用药剂，用于治疗由属于ESKAPE微生物的两种主要革兰氏阳性细菌引起的皮肤伤口感染。
