Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle, Germany.
Department of Medical Microbiology, University of Szeged, Dóm tér 10, 6720 Szeged, Hungary.
Med Chem. 2024;20(8):831-838. doi: 10.2174/0115734064302048240424045239.
The increasing antibacterial drug resistance remains a threat to global health with increasing mortality and morbidity. There is an urgent need to find novel antibacterials and develop alternative strategies to combat the increasing antibacterial drug resistance.
We aimed to synthesize novel small-molecule antibacterials to evaluate the structuredependent antibacterial compound activities against S. aureus and MRSA.
Compounds were synthesized by primary N-alkylation to form alkyl acridinium salts that were further functionalized with substituted phenyl residues and finally purified by column chromatography. The antibacterial growth inhibition activity was determined as MIC value.
The substituent effects on the determined antibacterial growth inhibitory properties have been discussed.
The best activities have been found for compounds with methoxy functions, exceeding the activities of reported novel antibacterial peptides. The compounds have also shown antibacterial drug-enhancing effects, which have been manifested as a reduction in the MIC values of the used antibiotics.
抗菌药物耐药性不断增加，导致死亡率和发病率上升，对全球健康构成威胁。因此迫切需要寻找新型抗菌药物并开发替代策略来应对日益增加的抗菌药物耐药性。
我们旨在合成新型小分子抗菌药物，以评估结构依赖性抗菌化合物对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌的活性。
通过初级 N-烷基化合成烷基吖啶盐，然后用取代的苯基残基进一步官能化，最后通过柱层析进行纯化。抗菌生长抑制活性通过 MIC 值确定。
讨论了取代基对确定的抗菌生长抑制特性的影响。
发现具有甲氧基功能的化合物具有最佳活性，超过了报道的新型抗菌肽的活性。这些化合物还表现出抗菌药物增强作用，表现为所用抗生素的 MIC 值降低。
