Medicinal Chemistry & Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, UK.
Molecules. 2022 Dec 20;28(1):5. doi: 10.3390/molecules28010005.
A series of benzyl, phenyl guanidine, and aminoguandine hydrazone derivatives was designed and in vitro antibacterial activities against two different bacterial strains ( and ) were determined. Several compounds showed potent inhibitory activity against the bacterial strains evaluated, with minimal inhibitory concentration (MIC) values in the low µg/mL range. Of all guanidine derivatives, 3-[2-chloro-3-(trifluoromethyl)]-benzyloxy derivative showed the best potency with MICs of 0.5 µg/mL () and 1 µg/mL (), respectively. Several aminoguanidine hydrazone derivatives also showed good overall activity. Compounds , , and - displayed MICs of 4 µg/mL against both and . In the aminoguanidine hydrazone series, 3-(4-trifluoromethyl)-benzyloxy derivative showed the best potency against (MIC 1 µg/mL) but was far less active against (MIC 16 µg/mL). Compound and the -substituted derivative also showed promising results against two strains of methicillin-resistant (MRSA). These results provide new and potent structural leads for further antibiotic optimisation strategies.
设计了一系列苄基、苯胍和氨基胍腙衍生物，并测定了它们对两种不同细菌（和）的体外抗菌活性。一些化合物对评价的细菌菌株表现出很强的抑制活性，最低抑菌浓度（MIC）值在低μg/mL 范围内。在所有胍衍生物中，3-[2-氯-3-（三氟甲基）]苄氧基衍生物表现出最好的活性，MIC 分别为 0.5μg/mL（）和 1μg/mL（）。一些氨基胍腙衍生物也表现出良好的整体活性。化合物、和的 MIC 分别为 4μg/mL，对和均有抑制作用。在氨基胍腙系列中，3-（4-三氟甲基）苄氧基衍生物对（MIC 1μg/mL）表现出最好的活性，但对（MIC 16μg/mL）的活性要差得多。化合物和取代的衍生物对两种耐甲氧西林金黄色葡萄球菌（MRSA）也表现出有希望的结果。这些结果为进一步的抗生素优化策略提供了新的、有效的结构先导。
