Derivatives of aryl-4-guanidinomethylbenzoate and N-aryl-4-guanidinomethylbenzamide as new antibacterial agents: synthesis and bioactivity

doi:10.1111/j.1745-7254.2008.00720.x

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	Derivatives of aryl-4-guanidinomethylbenzoate and N-aryl-4-guanidinomethylbenzamide as new antibacterial agents: synthesis and bioactivity
	Yu, Wen-yuan 2; Yang, Li-xia 2; Xie, Jian-shu 3; Zhou, Ling 2; Jiang, Xue-yuan 1; Zhu, De-xu 1; Muramatsu, Mutsumi 1; Wang, Ming-wei2
刊名	ACTA PHARMACOLOGICA SINICA
	2008-02
卷号	29 期号:2 页码:267-277
关键词	antibacterial agents drug-resistant bacteria Gram-positive bacteria
ISSN号	1671-4083
DOI	10.1111/j.1745-7254.2008.00720.x
文献子类	Article
英文摘要	Aim: The aim of the present study was to design, synthesize, and evaluate novel antibacterial agents, derivatives of aryl-4-guanidinomethylbenzoate and N-aryl-4-guanidinomethylbenzamide. Methods: A total of 44 derivatives of aryl-4-guanidinomethylbenzoate (series A) and N-aryl-4-guanidinomethylbenzamide (series B) were synthesized and their antibacterial activities were assessed in vitro against a variety of Gram-positive and Gram-negative bacteria by an agar dilution method. Results: Twelve compounds showed potent bactericidal effects against a panel of Gram-positive germs, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), vancomycin-intermediate Staphylococcus aureus (VISA), and methicillin-resistant coagulase-negative staphylococci (MRCNS), with minimum inhibitory concentrations (MIC) ranging between 0.5 and 8 mu g/mL, which were comparable to the MIC values of several marketed antibiotics. They exhibited weak or no activity on the Gram-negative bacteria tested. In addition, these compounds displayed high inhibitory activities towards oligopeptidase B of bacterial origin. Conclusion: In comparison with the previously reported MIC values of several known antibiotics, the derivatives of aryl-4-guanidinomethylbenzoate and N-aryl-4-guanidinomethylbenzamide showed comparable in vitro bactericidal activities against VRE and VISA as linezolid. Their growth inhibitory effects on MRSA were similar to vancomycin, but were less potent than linezolid and vancomycin against MRCNS. This class of compounds may have the potential to be developed into narrow spectrum antibacterial agents against certain drug-resistant strains of bacteria.
WOS关键词	NATURAL GUANIDINE DERIVATIVES ; RESISTANT STAPHYLOCOCCUS-AUREUS ; ACID 4-TERT-BUTYLPHENYL ESTER ; ESCHERICHIA-COLI ; OLIGOPEPTIDASE-B ; IN-VITRO ; ENTEROCOCCUS-FAECIUM ; HELICOBACTER-PYLORI ; TRYPSIN-INHIBITOR ; SIGNAL PEPTIDE
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:3249771
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000252805200019
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272983]
专题	国家新药筛选中心
通讯作者	Wang, Ming-wei
作者单位	1.Nanjing Univ, Dept Biochem, Nanjing 210093, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China; 3.Shanghai E Best Biopharmaceut Enterprises Co Ltd, Shanghai 200233, Peoples R China
推荐引用方式 GB/T 7714	Yu, Wen-yuan,Yang, Li-xia,Xie, Jian-shu,et al. Derivatives of aryl-4-guanidinomethylbenzoate and N-aryl-4-guanidinomethylbenzamide as new antibacterial agents: synthesis and bioactivity[J]. ACTA PHARMACOLOGICA SINICA,2008,29(2):267-277.
APA	Yu, Wen-yuan.,Yang, Li-xia.,Xie, Jian-shu.,Zhou, Ling.,Jiang, Xue-yuan.,...&Wang, Ming-wei.(2008).Derivatives of aryl-4-guanidinomethylbenzoate and N-aryl-4-guanidinomethylbenzamide as new antibacterial agents: synthesis and bioactivity.ACTA PHARMACOLOGICA SINICA,29(2),267-277.
MLA	Yu, Wen-yuan,et al."Derivatives of aryl-4-guanidinomethylbenzoate and N-aryl-4-guanidinomethylbenzamide as new antibacterial agents: synthesis and bioactivity".ACTA PHARMACOLOGICA SINICA 29.2(2008):267-277.