Copper-Catalyzed Synthesis, Bio-Evaluation, and in Silico Studies of 2-Aryl-N-alkylbenzimidazoles as Neuroprotective Agents

• Main Authors: Yun-Xin Yao, Nan-Nan Jia, Ya-Nan Cao, Xing-Xiu Chen, Feng Gao, Xiao-Xia Liang
• Format: Article
• Language: English
• Published: MDPI AG 2018-09-01
• Series: Catalysts
• Subjects: 2-arylbenzimidazoles; arylation; copper-catalysis; neuroprotective effect; molecular docking
• Online Access: http://www.mdpi.com/2073-4344/8/10/433

2-aryl-N-alkylbenzimidazole derivatives synthesized by CuI/PPh3 promoted direct coupling of N-alkylbenzimidazoles with aryl bromides. In vitro neurotoxicities of 20 compounds were evaluated, and the neuroprotective abilities of low-neurotoxic compounds (3b, 3g, 3h, 3i, 3j, 3k, 3o, 3q, 3s and 3t) were investigated against toxicity induced by 1-methyl-4-phenylpyridinium ion (MPP+) in SH-SY5Y neuronal cells. In silico studies revealed that compound 3g could have molecule docking with the following proteins: the bone morphogenetic protein receptor type 1B (BMPR1B), human cytochrome P450 1B1(CYP1B1), Metabotropic glutamate receptor 7 (GRM7), histone deacetylase 6 (HDAC6), 5-hydroxytryptamine receptor 5A (HTR5A), human topoisomerase II beta (TOP2B). A molecular docking simulation of model compound 3g and model protein CYP1B1 has been shown.