Główka Marek L, Kałużyńska Sylwia, Krause Malwina, Gobis Katarzyna, Foks Henryk, Szczesio Małgorzata, Olczak Andrzej
Institute of General and Ecological Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924 Łódź, Poland.
Department of Organic Chemistry, Medical University of Gdańsk, 107 Gen. Hallera, Ave., 80-416 Gdańsk, Poland.
Acta Crystallogr C Struct Chem. 2018 Dec 1;74(Pt 12):1684-1691. doi: 10.1107/S2053229618014675. Epub 2018 Nov 21.
Tuberculosis still remains a very important problem, especially its multidrug resistant varieties (MDR-TB). Among the potential tuberculostatics, there are two benzimidazole derivatives, namely 5,6-dimethyl-2-phenylethylbenzo[d]imidazole (1) and (E)-5,6-dimethyl-2-styryl-1H-benzo[d]imidazole (2) which showed significant tuberculostatic activities, better than those of Pyrazinamide and Isoniazyd. Also, the cytotoxicity of 1 appeared promising. The compounds were studied (with the use of X-ray diffraction) in the form of the hemihydrate of 1, CHN·0.5HO (1a), the methanol hemisolvate of 2, CHN·0.5CHOH (2a), and the acid oxalate salt of 2, namely (E)-5,6-dimethyl-2-styryl-1H-benzo[d]imidazolium hydrogen oxalate, CHN·CHO (2b). All three structures reveal a similar extended conformation, despite the flexible linker between the two aromatic systems and the different types of strong intermolecular hydrogen bonds. The molecules of 2a are practically planar due to the double bond in the linker, which enables conjugation along the whole molecule, while the molecules of 1a exhibit the possibility of parallel orientations of their aromatic systems, despite the aliphatic (ethyl) linker.
结核病仍然是一个非常重要的问题，尤其是其耐多药品种（耐多药结核病）。在潜在的抗结核药物中，有两种苯并咪唑衍生物，即5,6-二甲基-2-苯乙基苯并[d]咪唑（1）和（E）-5,6-二甲基-2-苯乙烯基-1H-苯并[d]咪唑（2），它们显示出显著的抗结核活性，优于吡嗪酰胺和异烟肼。此外，1的细胞毒性也很有前景。对这些化合物（使用X射线衍射）以1的半水合物CHN·0.5H₂O（1a）、2的甲醇半溶剂化物CHN·0.5CH₃OH（2a）以及2的草酸酸盐，即（E）-5,6-二甲基-2-苯乙烯基-1H-苯并[d]咪唑氢草酸酯CHN·C₂H₂O₄（2b）的形式进行了研究。尽管两个芳香体系之间存在柔性连接基且分子间氢键的类型不同，但所有三种结构都呈现出相似的伸展构象。由于连接基中的双键，2a的分子实际上是平面的，这使得整个分子能够发生共轭，而1a的分子尽管有脂肪族（乙基）连接基，但其芳香体系仍有可能呈现平行取向。
