Department of Chemistry & Centre for Advanced Studies in Chemistry, Panjab University, Chandigarh, 160014, India.
Department of Microbial Biotechnology, Panjab University, Chandigarh, 160014, India.
Eur J Med Chem. 2016 Nov 10;123:916-924. doi: 10.1016/j.ejmech.2016.07.076. Epub 2016 Aug 2.
A simple and efficient method has been described to synthesize the hitherto unknown imidazo[1,2-a]pyridine selenides (5a-l) by reaction of 2-chloroimidazo [1,2-a]pyridines with aryl/heteroaryl selenols, generated in situ by reduction of various diselenides with hypophosphorous acid. The crystal structures of 3-nitro-2-(phenylselanyl)-imidazo[1,2-a]pyridine (5a), 2-(mesitylselanyl)-3-nitro-imidazo[1,2-a]pyridine (5d) and 3-nitro-2-(pyridin-2-ylselanyl)-imidazo[1,2-a]pyridine (5e) were confirmed by X-ray crystallography and the DFT calculations were performed to determine various structural parameters which were correlated with the X-ray crystal structures. The synthesized compounds were subjected to antimicrobial evaluation and it was found that compounds 5a and 5j were active against gram negative bacterium Escherichia coli whereas compound 5e was active against different fungal strains. Time kill assay was performed to understand the microbial activity of synthesized organoselenium compounds and the toxicity of these compounds was evaluated against human cell lines. Synergistic effects of active compounds 5a and 5e were tested with existing antibiotic drugs which exhibited that the antibiotic combination with synthesized organoselenium compounds efficiently enhanced the antimicrobial activity.
已经描述了一种简单有效的方法来合成迄今未知的咪唑并[1,2-a]吡啶硒化物（5a-l），该方法是通过 2-氯咪唑并[1,2-a]吡啶与芳基/杂芳基硒醇反应得到的，后者是通过亚磷酸还原各种二硒化物原位生成的。通过 X 射线晶体学证实了 3-硝基-2-（苯基硒基）咪唑并[1,2-a]吡啶（5a）、2-（均三甲苯基硒基）-3-硝基-咪唑并[1,2-a]吡啶（5d）和 3-硝基-2-（吡啶-2-基硒基）咪唑并[1,2-a]吡啶（5e）的晶体结构，并进行了 DFT 计算以确定与 X 射线晶体结构相关的各种结构参数。对合成的化合物进行了抗菌评价，发现化合物 5a 和 5j 对革兰氏阴性菌大肠杆菌具有活性，而化合物 5e 对不同的真菌菌株具有活性。进行了时间杀伤试验以了解合成有机硒化合物的微生物活性，并评估了这些化合物对人细胞系的毒性。对活性化合物 5a 和 5e 进行了与现有抗生素药物的协同作用测试，结果表明，抗生素与合成有机硒化合物的组合可有效增强抗菌活性。
