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2,2,2-trifluoro-1-(1,4,5,6-tetrahydropyridin-3-yl)ethanone derivative as efflux pump inhibitor in Mycobacterium tuberculosis
Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2021-05-06 , DOI: 10.1016/j.bmcl.2021.128088
Priscila Cristina Bartolomeu Halicki 1 , Júlia Silveira Vianna 2 , Nilo Zanatta 3 , Valquiria Pereira de Andrade 3 , Mariana de Oliveira 4 , Malu Mateus 4 , Marcos Vinicius da Silva 4 , Virmondes Rodrigues 4 , Daniela Fernandes Ramos 1 , Pedro Eduardo Almeida da Silva 1
Affiliation  

Although the administration of combined therapy is efficient to tuberculosis (TB) treatment caused by susceptible Mycobacterium tuberculosis strains, to overcome the multidrug resistance is still a challenge. Some studies have reported evidence about tetrahydropyridines as a putative efflux pump inhibitor, including in mycobacteria, being a promising strategy against M. tuberculosis. Thus, we investigated the biological potential of 2,2,2-trifluoro-1-(1,4,5,6-tetrahydropyridin-3-yl)ethanone derivative (NUNL02) against two strains of M. tuberculosis. NUNL02 was able to increase the susceptibility of the multidrug resistant strain to the anti-TB drugs, resulting in synergism with rifampicin. Still, we assume that this compound plays a role in the efflux mechanism in M. tuberculosis, besides, to be able to kill the bacillus under the deprivation of essential nutrients. Thus, our findings highlight NUNL02 as a promising prototype to develop a new adjuvant for TB treatment, mainly as EPI.



中文翻译:

2,2,2-trifluoro-1-(1,4,5,6-tetrahydropyridin-3-yl)ethanone 衍生物作为结核分枝杆菌的外排泵抑制剂

尽管联合治疗对易感结核分枝杆菌菌株引起的结核病(TB)治疗有效,但克服多重耐药性仍然是一个挑战。一些研究报告了关于四氢吡啶作为推定的外排泵抑制剂的证据,包括在分枝杆菌中,是一种有希望的抗结核分枝杆菌策略。因此,我们研究了 2,2,2-trifluoro-1-(1,4,5,6-tetrahydropyridin-3-yl)ethanone 衍生物 (NUNL02) 对两种结核分枝杆菌菌株的生物学潜力. NUNL02 能够增加多重耐药菌株对抗结核药物的敏感性,从而与利福平产生协同作用。尽管如此,我们仍然假设这种化合物在结核分枝杆菌的外排机制中发挥作用,此外,能够在缺乏必需营养素的情况下杀死芽孢杆菌。因此,我们的研究结果突出了 NUNL02 作为开发新的结核病治疗佐剂(主要作为 EPI)的有前途的原型。

更新日期:2021-05-06
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