Synthesis, molecular modeling and biological evaluation of PSB as targeted antibiotics

被引：14

作者：

Cheng, Kui ^{[1
]}

Zheng, Qing-Zhong ^{[1
]}

Hou, Jin ^{[1
]}

Zhou, Yang ^{[1
]}

Liu, Chang-Hong ^{[1
]}

Zhao, Jing ^{[1
]}

Zhu, Hai-Liang ^{[1
]}

机构：

[1] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 07期

基金：

美国国家科学基金会;

关键词：

Peptide & Schiff base (PSB); ecKAS III; Antibacterial activity; Molecular modeling; SYNTHASE-III FABH; INHIBITOR; THIOLACTOMYCIN; DISCOVERY;

D O I：

10.1016/j.bmc.2010.02.052

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We described here the design, synthesis, molecular modeling, and biological evaluation of a series of peptide and Schiff bases (PSB) small molecules, inhibitors of Escherichia coli beta-Ketoacyl-acyl carrier protein synthase III (ecKAS III). The initial lead compound was reported by us previously, we continued to carry out structure-activity relationship studies and optimize the lead structure to potent inhibitors in this research. The results demonstrated that both N-(2-(3,5-dichloro-2-hydroxybenzylideneamino)propyl)2- hydroxybenzamide (1f) and 2-hydroxy-N-(2-(2-hydroxy-5-iodobenzylideneamino)propyl)-4-methylbenzamide (3e) posses good ecKAS III inhibitory activity and well binding affinities by bonding Gly152/Gly209 of ecKAS III and fit into the mouth of the substrate tunnel, and can be as potential antibiotics agent, displaying minimal inhibitory concentration values in the range 0.20-3.13 mu g/mL and 0.39-3.13 mu g/mL against various bacteria. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：2447 / 2455

页数：9

共 28 条

[1] Alkyl-CoA disulfides as inhibitors and mechanistic probes for FabH enzymes [J].

Alhamadsheh, Marnoun M. ;

Musayev, Faik ;

Komissarov, Andrey A. ;

Sachdeva, Sarbjot ;

Wright, H. Tonie ;

Scarsdale, Neel ;

Florova, Galina ;

Reynolds, Kevin A. .

CHEMISTRY & BIOLOGY, 2007, 14 (05) :513-524

[2] Biosynthetic origins of the natural product, thiolactomycin: A unique and selective inhibitor of type II dissociated fatty acid synthases [J].

Brown, MS ;

Akopiants, K ;

Resceck, DM ;

McArthur, HAI ;

McCormick, E ;

Reynolds, KA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2003, 125 (34) :10166-10167

[3] Synthesis, antibacterial activities and molecular docking studies of peptide and Schiff bases as targeted antibiotics [J].

Cheng, Kui ;

Zheng, Qing-Zhong ;

Qian, Yong ;

Shi, Lei ;

Zhao, Jing ;

Zhu, Hai-Liang .

BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (23) :7861-7871

[4] Structure of the human β-ketoacyl [ACP] synthase from the mitochondrial type II fatty acid synthase [J].

Christensen, Caspar Elo ;

Kragelund, Birthe B. ;

Von Wettstein-Knowles, Penny ;

Henriksen, Anette .

PROTEIN SCIENCE, 2007, 16 (02) :261-272

[5] Discovering Potent Inhibitors Against the β-Hydroxyacyl-Acyl Carrier Protein Dehydratase (FabZ) of Helicobacter pylori: Structure-Based Design, Synthesis, Bioassay, and Crystal Structure Determination [J].

He, Lingyan ;

Zhang, Liang ;

Liu, Xiaofeng ;

Li, Xianghua ;

Zheng, Mingyue ;

Li, Honglin ;

Yu, Kunqian ;

Chen, Kaixian ;

Shen, Xu ;

Jiang, Hualiang ;

Liu, Hong .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (08) :2465-2481

[6]

Heath Richard J, 2004, Curr Opin Investig Drugs, V5, P146

[7] Identification of critical staphylococcal genes using conditional phenotypes generated by antisense RNA [J].

Ji, YD ;

Zhang, B ;

Van Horn, SF ;

Warren, P ;

Woodnutt, G ;

Burnham, MKR ;

Rosenberg, M .

SCIENCE, 2001, 293 (5538) :2266-2269

[8] Analogues of thiolactomycin as potential antimalarial agents [J].

Jones, SM ;

Urch, JE ;

Kaiser, M ;

Brun, R ;

Harwood, JL ;

Berry, C ;

Gilbert, IH .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (19) :5932-5941

[9] Nature of copper(II)-lanthanide(III) magnetic interactions and generation of a large magnetic moment with magnetic anisotropy of 3d-4f cyclic cylindrical tetranuclear complexes [CuIILLnIII(hfaC)2]2, (H3L=1-(2-hydroxybenzamido)-2-(2-hydroxy-3-methoxybenzylideneamino)ethane and Hhfac = hexafluoroacetylacetone, LnIII = Eu, Gd, Tb, Dy) [J].

Kido, T ;

Ikuta, Y ;

Sunatsuki, Y ;

Ogawa, Y ;

Matsumoto, N .

INORGANIC CHEMISTRY, 2003, 42 (02) :398-408

[10] β-ketoacyl-acyl carrier protein synthase III (FabH) is essential for bacterial fatty acid synthesis [J].

Lai, CY ;

Cronan, JE .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (51) :51494-51503

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