Towards eradicating antibiotic-resistant bacteria: synthesis and antibacterial activities of substituted N-(2-nitrophenyl)pyrrolidine-and piperidine-2-carboxylic acids

• 来源期刊: 中国药学（英文版）
• 学科: 医学
• 年，卷（期）: 2019,（10）
• 所属期刊栏目: 研究论文
• 页码范围: 704-715
• 页数: 12页
• 分类号: R914
• 语种: 英文

摘要

Antibacterial resistance is a source of great concern in the effective prevention and treatment of infections caused by bacteria,making the development of requisite therapeutics a major challenge.N-(Nitrophenyl)cycloamino acids are important compounds in the synthesis of poly-condensed nitrogen-containing heterocycles with marked activities in many biological systems.A series of substituted N-(o-nitrophenyl)cycloamino-2-carboxylic acids 3a-3g were synthesized via the condensation reaction of substituted o-halogenonitrobenzenes with L-proline 2a and D,L-pipecolinic acid 2b,under refluxing alcoholic basic conditions in excellent yields.The synthesized compounds were characterised by FT-IR,(1H & 13C) NMR,UV-Vis,mass spectroscopy and elemental analysis.Their antibacterial activities were evaluated against five Gram-positive and five Gram-negative bacterial strains using the broth micro-dilution procedure.The antibacterial activities of the synthesized compounds were compared with streptomycin and nalidixic acid as standard antibiotic drugs.The minimum inhibitory concentration (MIC) values of compounds 3a-3g revealed good antibacterial activities against the tested microorganisms.Compounds 3a-3g were more potent than nalidixic acid against Enterococcusfaecalis,Mycobacterium smegmatis,Escherichia coli and Proteus vulgaris and also more potent than streptomycin against Enterobacter cloacae and Staphylococcus aureus.Compounds 3a,3c and 3g displayed the highest antibacterial potency with an MIC value of 15.6 μg/mL against E.cloacae,E.faecalis and P.mirabilis,respectively.These results indicated that these aryl cycloamino acids with antibacterial activities had potential applications as substitutes for antimicrobial peptide antibiotics,which are not susceptible to bacterial resistance,to solve the problem of drug resistance.