A simple and environment friendly one-pot synthesis of ethyl 3,5-dicyano-6-oxo-2,4-diarylpiperidine-3-carboxylate derivatives from aryl aldehydes, ethyl cyanoacetate, and ammonium acetate was developed in aqueous medium without using a catalyst. The significant features of this method are easy, inexpensive experimental procedures with short reaction time and high yield. The use of water as the solvent without catalyst makes the reaction meritorious and further fulfilled green chemistry protocols. The compounds were screened for antibacterial activity against Gram-positive bacteria (Staphylococcus aureus 25923) and Gram-negative bacteria (Escherichia coli ATCC25922) by disk diffusion method. Compounds 4f, 4h, and 4i showed moderate antibacterial activity S. aureus. Intriguingly, compound 4g exhibited very good antibacterial activity against E. coli. Antitubercular activity assay indicates that the compounds 4(a–c) exhibited activity with varying MICs against mycobacterium tuberculosis H37RV control strain and multidrug-resistant tuberculosis (MDR-TB) clinical isolate. Among the three tested compounds, 4c showed an equipotent antitubercular activity against H37Rv and MDR-TB clinical isolates with MIC 3.13 μg/ml. Further, docking analysis of synthesized piperidinone derivatives with acetate kinase protein reported that these compounds interact effectively with the catalytic residues that are in the vicinity of ATP binding and active sites facilitating inhibition of enzyme function. Thus these derivatives can be promising compounds for antitubercular activity to combat tuberculosis.

中文翻译：

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3,5-二氰基-6-氧代-2,4-二芳基哌啶-3-羧酸乙酯衍生物的绿色合成，抗结核评估和分子对接研究

在不使用催化剂的情况下，在水性介质中开发了一种简单且环境友好的一锅合成法，该方法由芳基醛，氰基乙酸乙酯和乙酸铵合成3,5-二氰基-6-氧代-2,4-二芳基哌啶-3-羧酸乙酯衍生物。该方法的显着特点是简单，廉价的实验步骤，反应时间短，产率高。在没有催化剂的情况下使用水作为溶剂使得该反应是值得的并且进一步满足了绿色化学方案。通过盘扩散法筛选化合物对革兰氏阳性菌（金黄色葡萄球菌25923）和革兰氏阴性菌（大肠杆菌ATCC25922）的抗菌活性。化合物4f，4h和4i表现出中等的抗菌活性金黄色葡萄球菌。有趣的是，化合物4g对大肠杆菌表现出非常好的抗菌活性。抗结核活性测定表明，化合物4（a-c）对MIC结核分枝杆菌H37RV对照菌株和耐多药结核病（MDR-TB）临床分离株具有不同的MIC 。在三种测试化合物中，4cMIC 3.13μg/ ml对H37Rv和MDR-TB临床分离株具有同等的抗结核活性。此外，合成的哌啶酮衍生物与乙酸激酶蛋白的对接分析表明，这些化合物与ATP结合附近的催化残基和活性位点有效相互作用，从而促进酶功能的抑制。因此，这些衍生物可能是有希望的抗结核活性化合物，以抗击结核病。