Bastos Mírian Letícia Carmo, Adido Houéfa Egidia Fallon, Martins de Brito Ananda Karolyne, Chagas Cristian Kallahan Silva, Castro Ana Laura Gadelha, Ferreira Gleison Gonçalves, Nascimento Pedro Henrique Costa, Padilha Walice Rans da Silva, Sarmento Rosana Moura, Garcia Viviane Vasconcelos, Marinho Andrey Moacir do Rosario, Marinho Patrícia Santana Barbosa, Rocha de Oliveira Johnatt Allan, Vale Valdicley Vieira, Percário Sandro, Dolabela Maria Fâni
Biodiversity and Biotechnology Bionorte Network, Federal University of Para, Belém 66075-110, PA, Brazil.
Faculty of Pharmacy, Federal University of Para, Belém 66075-110, PA, Brazil.
Int J Mol Sci. 2024 Nov 23;25(23):12583. doi: 10.3390/ijms252312583.
Naphthoquinones eleutherin and isoeleutherin have demonstrated promising antibacterial activity, probably due to their quinone structure, which can generate reactive oxygen species. The study examines the activities of pathogens, such as and , associated with antimicrobial resistance and explores their potential mechanisms of action. The MIC, IC, and MBC were determined. PharmMapper 2017 server and GOLD 2020.1 software were utilized for molecular docking to identify protein targets and interaction mechanisms. The docking predictions were verified by redocking, focusing on structures with RMSD below 2 Å. The molecular docking revealed a significant affinity of eleutherin for the peptide, transcriptional regulator QacR, and regulatory protein BlaR1 with better interactions with BlaR1 than the crystallographic ligand (benzylpenicillin). Isoeleutherin demonstrated specific interactions with methionine aminopeptidase, indicating specificity and affinity. In summary, the difference in naphthoquinones activities may be related to structural differences. Eleutherin exhibits potential as a therapeutic adjuvant to reverse bacterial resistance in , suggesting this molecule interferes with the antibiotic resistance mechanism. The absence of homologous proteins or variations in the structure of the target proteins could be the cause of the inactivity against .
萘醌类化合物刺蒺藜素和异刺蒺藜素已显示出有前景的抗菌活性，这可能归因于它们的醌结构，该结构可产生活性氧物种。该研究考察了与抗菌抗性相关的病原体（如[具体病原体未给出]）的活性，并探索了它们潜在的作用机制。测定了最低抑菌浓度（MIC）、半数抑制浓度（IC）和最低杀菌浓度（MBC）。利用PharmMapper 2017服务器和GOLD 2020.1软件进行分子对接，以确定蛋白质靶点和相互作用机制。通过重新对接验证对接预测，重点关注均方根偏差（RMSD）低于2 Å的结构。分子对接显示刺蒺藜素对肽、转录调节因子QacR和调节蛋白BlaR1具有显著亲和力，与BlaR1的相互作用比晶体学配体（苄青霉素）更好。异刺蒺藜素与甲硫氨酸氨肽酶表现出特异性相互作用，表明具有特异性和亲和力。总之，萘醌类化合物活性的差异可能与结构差异有关。刺蒺藜素作为一种治疗佐剂，在[具体情况未明确]中具有逆转细菌抗性的潜力，表明该分子干扰了抗生素抗性机制。缺乏同源蛋白或靶蛋白结构的变异可能是对[具体对象未明确]无活性的原因。
