Nguyen Dao Dinh, Duong Thuc-Huy, Nguyen Thi-Phuong, Nguyen Huy Truong, Nguyen Chuong Hoang
Faculty of Biology-Biotechnology, University of Science, Vietnam National University Ho Chi Minh City, 227 Nguyen Van Cu, District 5, Ho Chi Minh City 749000, Vietnam.
Department of Chemistry, Ho Chi Minh City University of Education, 280 An Duong Vuong, District 5, Ho Chi Minh City 748342, Vietnam.
ACS Omega. 2024 Dec 3;9(50):50012-50023. doi: 10.1021/acsomega.4c09518. eCollection 2024 Dec 17.
is a human pathogen responsible for a variety of diseases, from skin, soft tissue, and lung infections to severe cases such as meningitis, infective endocarditis, and bacteremia. The high level of antibiotic resistance in these pathogens, exemplified by methicillin-resistant (MRSA), necessitates the development of effective antibiotics. Thus, this work introduced the chemical synthesis of ethyl 3,5-dibromoorsellinate, a derivative of ethyl orsellinate from the lichen mycobiont of , and its effectiveness against MRSA was assessed. Results showed that ethyl 3,5-dibromoorsellinate efficiently inhibited MRSA with a minimum inhibitory concentration (MIC) of 4 μg/mL, and the time-kill analysis showed the bactericidal effect of ethyl 3,5-dibromoorsellinate on MRSA at 8× MIC after 24 h. The compound also exhibited selective activity against MRSA compared with the human cell line, with a selectivity index of 12.5-fold. While ethyl 3,5-dibromoorsellinate exhibited an indifferent effect with ampicillin, this compound demonstrated antagonistic effects with kanamycin in the synergistic assessment. Additionally, ethyl 3,5-dibromoorsellinate demonstrated antibiofilm activity against MRSA starting from 0.25× MIC. The molecular docking investigation illustrated that ethyl 3,5-dibromoorsellinate binds with the penicillin-binding protein 2A of MRSA with a free energy of -42.5 to -45.7 kcal/mol. Given its promising antibacterial activities, ethyl 3,5-dibromoorsellinate warrants further investigation as a potential antibiotic option against MRSA.
是一种人类病原体，可引发多种疾病，从皮肤、软组织和肺部感染到严重病例，如脑膜炎、感染性心内膜炎和菌血症。这些病原体中的高水平抗生素耐药性，以耐甲氧西林（MRSA）为例，使得开发有效的抗生素成为必要。因此，这项工作介绍了3,5 - 二溴苔色酸乙酯的化学合成，它是地衣共生菌苔色酸乙酯的衍生物，并评估了其对MRSA的有效性。结果表明，3,5 - 二溴苔色酸乙酯以4μg/mL的最低抑菌浓度有效抑制MRSA，时间杀菌分析表明，24小时后，3,5 - 二溴苔色酸乙酯在8倍MIC时对MRSA有杀菌作用。与人类细胞系相比，该化合物对MRSA也表现出选择性活性，选择性指数为12.5倍。虽然3,5 - 二溴苔色酸乙酯与氨苄西林表现出无关作用，但在协同评估中，该化合物与卡那霉素表现出拮抗作用。此外，3,5 - 二溴苔色酸乙酯从0.25倍MIC开始就对MRSA表现出抗生物膜活性。分子对接研究表明，3,5 - 二溴苔色酸乙酯与MRSA的青霉素结合蛋白2A结合，自由能为 - 42.5至 - 45.7 kcal/mol。鉴于其有前景的抗菌活性，3,5 - 二溴苔色酸乙酯作为一种潜在的抗MRSA抗生素选择值得进一步研究。
