Energy Engineering College, Yulin University, Yulin City-719000, P. R. China.
School of New Energy, Yulin University, Yulin 719000, Shaanxi, P. R. China.
Bioorg Chem. 2024 Feb;143:106975. doi: 10.1016/j.bioorg.2023.106975. Epub 2023 Nov 18.
The rapid spread of Methicillin-resistant Staphylococcus aureus (MRSA) and its difficult-to-treat skin and filmsy diseases are making MRSA a threat to human life. The most dangerous feature is the fast emergence of MRSA resistance to all recognized antibiotics, including vancomycin. The creation of novel, effective, and non-toxic drug candidates to combat MRSA isolates is urgently required. Fluorine containing small molecules have taken a centre stage in the field of drug development. Over the last 50 years, there have been a growing number of fluorinated compounds that have been approved since the clinical usage of fluorinated corticosteroids in the 1950 s and fluoroquinolones in the 1980 s. Due to its advantages in terms of potency and ADME (absorption, distribution, metabolism, and excretion), fluoro-pharmaceuticals have been regarded as a potent and useful tool in the rational drug design method. The flexible bioactive fluorinated azoles are ideal candidates for the development of new antibiotics. This review summarizes the decade developments of fluorinated azole derivatives with a wide antibacterial activity against diverged MRSA strains. In specific, we correlated the efficacy of structurally varied fluorinated azole analogues including thiazole, benzimidazole, oxadiazole and pyrazole against MRSA and discussed different angles of structure-activity relationship (SAR).
耐甲氧西林金黄色葡萄球菌(MRSA)的迅速传播及其难以治疗的皮肤和脆弱疾病,使 MRSA 对人类生命构成威胁。最危险的特征是 MRSA 对所有公认的抗生素(包括万古霉素)迅速产生耐药性。迫切需要开发新型、有效且无毒的药物候选物来对抗 MRSA 分离株。含氟小分子在药物开发领域占据了中心地位。在过去的 50 年中,自 20 世纪 50 年代氟皮质激素和 80 年代氟喹诺酮类药物开始临床应用以来,已有越来越多的含氟化合物被批准用于临床。由于其在效力和 ADME(吸收、分布、代谢和排泄)方面的优势,氟药物已被视为合理药物设计方法中的有力且有用的工具。灵活的生物活性氟唑类化合物是开发新型抗生素的理想候选物。本综述总结了过去十年中具有广泛抗不同 MRSA 菌株的抗菌活性的氟化唑衍生物的研究进展。具体而言,我们将结构各异的氟化唑类似物(包括噻唑、苯并咪唑、恶二唑和吡唑)对 MRSA 的功效进行了关联,并讨论了不同的构效关系(SAR)角度。