European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2013-01-23 , DOI: 10.1016/j.ejmech.2012.12.055 Navin B. Patel , Amit C. Purohit , Dhanji P. Rajani , Rosa Moo-Puc , Gildardo Rivera
A novel series of 5-(2-benzylsulfanyl-pyridin-3-yl)-2-(substituted)-sulfanyl-1,3,4-oxadiazoles 6a–j were synthesized from key intermediate 5-(2-benzylsulfanyl-pyridin-3-yl)-3H-[1,3,4]oxadiazole-2-thione 5. Nucleophilic substitution reactions with different electrophiles (E+), such as haloacetate and haloalkyl groups, were performed to get target compounds 6a–j. Compounds were characterized by NMR, mass, IR spectra and C, H, N analyses. All compounds were evaluated for their antimicrobial and antimycobacterial activities; selected analogs were screened for their anticancer activity on 60 tumor cell lines at single dose 1.00−5 M. Unfortunately, none of the compounds showed a significant antitumor activity on 60 human tumor cell lines. However, compounds 6g and 6f with benzothiazole moiety (12.5 and 25 μg/ml) showed promising activity against Escherichia coli compared to ampicillin; compounds 6d, 6j bearing triazole and morpholine, respectively, showed promising antitubercular activity (25 μg/ml) compared to rifampicin.
中文翻译:
基于2-苄基硫烷基烟酸的1,3,4-恶二唑类化合物的合成及生物学评价
从关键中间体5-(2-苄基硫烷基-吡啶- )合成了一系列新的5-(2-苄基硫烷基-吡啶-3-基)-2-(取代)-硫烷基-1,3,4-恶二唑6a – j。 3-(基)-3 H- [1,3,4]恶二唑-2-硫酮5。进行了不同亲电子试剂(E +)的亲核取代反应,例如卤代乙酸酯和卤代烷基,从而得到目标化合物6a – j。通过NMR,质谱,IR光谱和C,H,N分析来表征化合物。对所有化合物的抗微生物和抗分枝杆菌活性进行了评估。筛选选定的类似物以单剂量1.00 -5对60种肿瘤细胞系的抗癌活性 M.不幸的是,没有一种化合物对60种人类肿瘤细胞系显示出显着的抗肿瘤活性。然而,与氨苄西林相比,具有苯并噻唑部分(分别为12.5和25μg/ ml)的化合物6g和6f对大肠杆菌表现出令人鼓舞的活性。与利福平相比,分别带有三唑和吗啉的化合物6d,6j显示出有希望的抗结核活性(25μg/ ml)。