Balandis Benas, Kavaliauskas Povilas, Grybaitė Birutė, Petraitis Vidmantas, Petraitienė Rūta, Naing Ethan, Garcia Andrew, Grigalevičiūtė Ramunė, Mickevičius Vytautas
Department of Organic Chemistry, Kaunas University of Technology, Radvilėnų Rd. 19, LT-50254 Kaunas, Lithuania.
Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, 1300 York Ave., New York, NY 10065, USA.
Microorganisms. 2023 Apr 3;11(4):935. doi: 10.3390/microorganisms11040935.
Infections caused by drug-resistant (DR) () complex (MAC) are an important public health concern, particularly when affecting individuals with various immunodeficiencies or chronic pulmonary diseases. Rapidly growing antimicrobial resistance among MAC urges us to develop novel antimicrobial candidates for future optimization. Therefore, we have designed and synthesized benzenesulfonamide-bearing functionalized imidazole or alkylated derivatives and evaluated their antimicrobial activity using multidrug-resistant strains and compared their antimycobacterial activity using BCG and H37Ra. Benzenesulfonamide-bearing imidazole-2-thiol compound containing 4-CF substituent in benzene ring, showed strong antimicrobial activity against the tested mycobacterial strains and was more active than some antibiotics used as a reference. Furthermore, an imidazole-bearing 4-F substituent and S-methyl group demonstrated good antimicrobial activity against complex strains, as well as BCG and H37Ra. In summary, these results demonstrated that novel benzenesulfonamide derivatives, bearing substituted imidazoles, could be further explored as potential candidates for the further hit-to-lead optimization of novel antimycobacterial compounds.
由耐药性（DR）鸟分枝杆菌复合群（MAC）引起的感染是一个重要的公共卫生问题，尤其是当感染影响到各种免疫缺陷或慢性肺部疾病患者时。MAC中迅速增长的抗菌耐药性促使我们开发新型抗菌候选药物以供未来优化。因此，我们设计并合成了带有苯磺酰胺的功能化咪唑或烷基化衍生物，并使用多重耐药菌株评估了它们的抗菌活性，还使用卡介苗（BCG）和H37Ra比较了它们的抗分枝杆菌活性。在苯环上含有4-CF取代基的带有苯磺酰胺的咪唑-2-硫醇化合物，对测试的分枝杆菌菌株显示出强大的抗菌活性，并且比用作参考的一些抗生素更具活性。此外，带有4-F取代基和S-甲基的咪唑对MAC复合菌株以及卡介苗和H37Ra都表现出良好的抗菌活性。总之，这些结果表明，带有取代咪唑的新型苯磺酰胺衍生物可作为新型抗分枝杆菌化合物进一步从苗头化合物到先导化合物优化的潜在候选物进行进一步探索。
