Postgraduate Program in Bioscience & Physiopathology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil.
Laboratory of Medical Bacteriology, Department of Clinical Analysis & Biomedicine, State University of Maringa, Parana, Brazil.
Future Microbiol. 2019 Mar;14:331-344. doi: 10.2217/fmb-2018-0333. Epub 2019 Feb 13.
To evaluate (i) the in vitro activity of eugenol (EUG) and three derivatives against Mycobacterium tuberculosis (Mtb), nontuberculous mycobacteria (NTM) and other bacteria, (ii) the EUG and antituberculosis drugs combinatory effect and (iii) the EUG and its derivatives cytotoxicity.
MATERIALS & METHODS: Minimum inhibitory concentration of the compounds were determined by resazurin microtiter or broth microdilution assay and the drug interaction between EUG and antituberculosis drugs by resazurin drug combination microtiter. The cytotoxicity was carried out in macrophages, HeLa and VERO cells. Results: EUG and derivatives displayed activity and synergic effect of EUG combined with rifampicin, isoniazid, ethambutol, and pyrazinamide in Mtb including multidrug-resistant isolates, with more selectivity to bacillus than macrophages, HeLa and VERO cells (selective index from 0.65 to 31.4). EUG derivatives (4-allyl-2-methoxyphenyl acetate, 4-allyl-2-methoxyphenyl benzoate, and 4-allyl-2-methoxyphenyl 4-nitrobenzoate) were more active against nontuberculous mycobacteria than EUG. EUG and derivatives exhibited low activity in other Gram-positive and -negative bacteria.
EUG and its derivatives show activity against Mycobacterium spp. and synergic effect of EUG combined with antituberculosis drugs against Mtb.
（i）评估丁香酚（EUG）及其三种衍生物对结核分枝杆菌（Mtb）、非结核分枝杆菌（NTM）和其他细菌的体外活性；（ii）EUG 与抗结核药物联合作用；（iii）EUG 及其衍生物的细胞毒性。
采用 Resazurin 微量肉汤稀释法测定化合物的最小抑菌浓度，采用 Resazurin 药物联合微量稀释法测定 EUG 与抗结核药物的相互作用。在巨噬细胞、HeLa 和 VERO 细胞中进行细胞毒性实验。
EUG 及其衍生物对 Mtb（包括耐多药株）具有活性和协同作用，与利福平、异烟肼、乙胺丁醇和吡嗪酰胺联合使用时，对杆菌的选择性高于巨噬细胞、HeLa 和 VERO 细胞（选择性指数为 0.65 至 31.4）。EUG 衍生物（4-烯丙基-2-甲氧基苯基乙酸酯、4-烯丙基-2-甲氧基苯基苯甲酸酯和 4-烯丙基-2-甲氧基苯基 4-硝基苯甲酸酯）对非结核分枝杆菌的活性高于 EUG。EUG 及其衍生物对其他革兰氏阳性和阴性菌的活性较低。
EUG 及其衍生物对分枝杆菌属具有活性，EUG 与抗结核药物联合使用对 Mtb 具有协同作用。
