Gobis Katarzyna, Foks Henryk, Suchan Karolina, Augustynowicz-Kopeć Ewa, Napiórkowska Agnieszka, Bojanowski Krzysztof
Department of Organic Chemistry, Medical University of Gdańsk, 107 Gen. Hallera Ave., 80-416 Gdańsk, Poland.
Department of Organic Chemistry, Medical University of Gdańsk, 107 Gen. Hallera Ave., 80-416 Gdańsk, Poland.
Bioorg Med Chem. 2015 May 1;23(9):2112-20. doi: 10.1016/j.bmc.2015.03.008. Epub 2015 Mar 9.
A series of novel 2-(2-phenalkyl)-1H-benzo[d]imidazole derivatives and analogues (2a-3l) have been synthesized and evaluated for tuberculostatic activity. Benzimidazoles substituted at the C-2 position with phenethyl, styryl and 3,5-dichlorophenethyl moiety were obtained. Compounds 2g, 2h and 2i bearing methyl groups at the benzimidazole system and phenalkyl substituent at the C-2 position showed high tuberculostatic activity against Mycobacterium tuberculosis strains with MIC values ranging from 0.8 to 6.2 μg/mL (2.5-25 μM). More importantly, derivatives 2g (5,6-dimethyl-2-phenethyl-1H-benzo[d]imidazole) and 2i (2-(3,5-dichlorophenethyl)-5,6-dimethyl-1H-benzo[d]imidazole) appeared selective for M. tuberculosis as compared with eukaryotic cells: non-malignant (neonatal human dermal fibroblasts) and malignant (mouse melanoma B16-F10 cell line). These compounds may thus represent a novel, selective class of anti-tubercular agents. SAR studies resulted in interesting conclusions on structural factors affecting tuberculostatic activity.
已合成了一系列新型的2-(2-苯烷基)-1H-苯并[d]咪唑衍生物及其类似物(2a - 3l)，并对其抑菌活性进行了评估。得到了在C-2位被苯乙基、苯乙烯基和3,5-二氯苯乙基部分取代的苯并咪唑。在苯并咪唑体系带有甲基且在C-2位带有苯烷基取代基的化合物2g、2h和2i对结核分枝杆菌菌株表现出高抑菌活性，其最低抑菌浓度(MIC)值范围为0.8至6.2 μg/mL(2.5 - 25 μM)。更重要的是，与真核细胞(非恶性的新生人类皮肤成纤维细胞和恶性的小鼠黑色素瘤B16-F10细胞系)相比，衍生物2g(5,6-二甲基-2-苯乙基-1H-苯并[d]咪唑)和2i(2-(3,5-二氯苯乙基)-5,6-二甲基-1H-苯并[d]咪唑)对结核分枝杆菌具有选择性。因此，这些化合物可能代表一类新型的选择性抗结核药物。构效关系研究得出了关于影响抑菌活性的结构因素的有趣结论。
