Corrêa Barros Lélia Pacheco, Del Rio Karina Pena, Carvalho Tatiane Dos Santos Conceição, Pinto Maria do Carmo Freire Ribeiro, de Moura Kelly Cristina Gallan, Halicki Priscila Cristina Bartolomeu, Ramos Daniela Fernandes, da Silva Pedro Eduardo Almeida
Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande - FURG, Rua General Osório, s/nº, Centro, CEP 96.200-400, Rio Grande, RS, Brazil.
Instituto de Pesquisas em Produtos Naturais, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Tuberculosis (Edinb). 2018 Jul;111:198-201. doi: 10.1016/j.tube.2018.06.015. Epub 2018 Jul 3.
Tuberculosis (TB) is the cause of more than one million deaths worldwide, and despite being a curable disease, some factors can make therapy difficult, emphasizing the need for the development of new drugs that may potentiate the action of the classic anti-TB antimicrobials. Naphthoimidazoles show a broad spectrum of biological activities, including antimycobacterial activity. The aim of this study was to evaluate the anti-Mycobacterium tuberculosis activity of nine naphthoimidazoles, alone and combined with isoniazid (INH) and rifampicin (RIF). We evaluated the minimum inhibitory concentration (MIC) of the compounds, the fractional inhibitory concentration of the combinations of the naphthoimidazoles with INH or RIF, and the cytotoxicity of these compounds. Eight compounds showed MICs ranging from 1.56 to 25 μg/mL and the presence of substituents on phenyl groups shown to be essential for antimycobacterial activity. Four compounds showed additivity with both INH and RIF and showed SI values higher than 10, indicating safety. Thus, considering the antimycobacterial activity and the absence of antagonism between naphthoimidazoles and the two main drugs for TB treatment, these compounds could be scaffolds for the development of new anti-TB drugs.
结核病（TB）在全球范围内导致了超过100万人死亡，尽管它是一种可治愈的疾病，但一些因素会使治疗变得困难，这凸显了开发可能增强经典抗结核抗菌药物作用的新药的必要性。萘并咪唑类化合物具有广泛的生物活性，包括抗分枝杆菌活性。本研究的目的是评估9种萘并咪唑类化合物单独以及与异烟肼（INH）和利福平（RIF）联合使用时对结核分枝杆菌的活性。我们评估了这些化合物的最低抑菌浓度（MIC）、萘并咪唑类化合物与INH或RIF组合的部分抑菌浓度，以及这些化合物的细胞毒性。8种化合物的MIC范围为1.56至25μg/mL，且苯环上的取代基显示对抗分枝杆菌活性至关重要。4种化合物与INH和RIF均表现出相加作用，且安全指数（SI）值高于10，表明具有安全性。因此，考虑到萘并咪唑类化合物的抗分枝杆菌活性以及与两种主要抗结核药物之间不存在拮抗作用，这些化合物可能成为开发新型抗结核药物的骨架。
