CN104292127B - Biomembranous formation is suppressed containing N-nitrobenzophenone amides compound - Google Patents
Biomembranous formation is suppressed containing N-nitrobenzophenone amides compound Download PDFInfo
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- CN104292127B CN104292127B CN201410448729.5A CN201410448729A CN104292127B CN 104292127 B CN104292127 B CN 104292127B CN 201410448729 A CN201410448729 A CN 201410448729A CN 104292127 B CN104292127 B CN 104292127B
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- nitrobenzophenone
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- biomembranous formation
- amides compound
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Abstract
The invention discloses and there is structure containing the biomembranous formation of suppression of N-phenylamide compound, for the application of antibiotic synergist. This compounds is felt effect by biological group and is suppressed biomembranous formation, it is possible to increase antibiotic effect.
Description
Technical field
The present invention is that a nitrobenzophenone amides compound containing N-can suppress microorganism to form biomembrane, thus being applied to antibiotic synergist.
Background technology
Bacterial biof iotalm is that antibacterial is wrapped in the polymer (mainly polysaccharide) of self secretion, a kind of bacterial community with stereochemical structure of formation. Biomembrane has barrier action, it is impossible to penetrate biomembranous antibiotic, it is difficult to contacts with the antibacterial in biomembrane or is difficult to reach antibacterial required concentration, thus cannot play the effect of bacteriostasis and sterilization. Refractory microorganism infection more than 60% is relevant with the formation of bacterial biof iotalm according to estimates. Bacterial biof iotalm is once be formed, and its drug resistance can improve hundreds and thousands of times, is clinical infection obstinate, the pathogen major reason that is difficult to thoroughly removing. Suppress biomembranous generation will be effectively improved antibiotic effect.
Bacterial biof iotalm is formed can be affected by multiple environmental factor, though not yet illustrating completely at present, but bacterial community induction system (quorumsensing, QS) is considered as the key link in biofilm formation process, directly affects the formation of bacterial biof iotalm and dissociates. Intervention school-based is mainly made up of las system, rhl system and QscR system, and wherein the transcriptional expression promoting downstream gene is conducive to biomembranous formation by induction las system, and las system is had inhibitory action by QscR system. Therefore, it is suppressed that las system induction and activation QscR system are by the formation of double inhibition bacterial biof iotalm.
Summary of the invention
This patent builds its Pharmacophore Model respectively based on las derivant complex, las inhibitor complexes and QscR derivant complex. And for suppressing las induction and activating QscR feature, screen from the compound library containing 167740, it was found that there is the active compound QLT-2 suppressing bacterial biof iotalm to be formed.
The method of the present invention can be used for biomembrane formation inhibitor, thus being applied to antibiotic synergist.
This patent relates to the nitrobenzophenone amides compound structural formula containing N-
The method of the present invention can suppress Pseudomonas aeruginosa (pseudomonasaeruginosa, PA) biomembranous generation, reduce the drug resistance of PA and pathogenic, can be used for the auxiliary treatment of the diseases such as PA bacteremia, pneumonia, urinary system infection, burn infection and the cystic fibrosis secondary infection caused.
In order to prove that the present invention suppresses the effect of PA biofilm formation, compound sample is carried out following pharmacological testing.
Medicine and reagent
Sample
Weighing a certain amount of medicine, add a small amount of DMSO and dissolve, preparation obtains medicine storage stock solution, preserves in the refrigerator of less than-20 DEG C, and storage life is less than half a year. By LB broth dilution medicine storage stock solution, the Concentraton gradient of institute's reference is according to the MIC result of gained, so gained concentration is 1/2MIC, 1/4MIC, 1/8MIC, 1/16MIC, namely the Concentraton gradient of all medicines is 128ug/ml, 64ug/ml, 32ug/ml, 16ug/ml, and the Concentraton gradient of positive drug bromo-furanone is 64ug/ml, 32ug/ml, 16ug/ml, 8ug/ml. The medicine of series concentration is now with the current.
Experiment antibacterial
Weigh 2.1gLB broth bouillon powder, and be dissolved in 100ml deionized water, 121 DEG C of autoclaving 40min, it is cooled to room temperature, in-4 DEG C of preservations. After recovery Pseudomonas aeruginosa ATCC27853 and fastbacteria Pseudomonas aeruginosa, by LB culture medium bacterium solution is diluted to 0.5MCF (bacterial population is about 1～2*108CFU/mL), with LB meat soup, above-mentioned bacterium solution is diluted (1: 1000), now with the current. Bacterium solution after dilution must be inoculated complete in 20min.
96 orifice plate 1-7 row (respectively containing 12 holes) are separately added into the corresponding medicinal liquid of 100ul, inoculating above-mentioned bacterium solution 100ul, the 8th row set 6 holes respectively and arrange negative control group (each 100ul of LB culture medium, bacterium solution) and blank group (LB culture medium 200ul); Cultivate after 20h in 37 DEG C of constant incubators, be directly added into after the crystal violet solution (20ul) that concentration is 0.5% carries out dyeing 20min, suck crystal violet solution; Add 250ul95% ethanol to dissolve biomembrane-crystal violet complex, and measure every hole light absorption value (OD) at 630nm wavelength place by microplate reader; Parallel assay three times, result represents with biomembrane suppression ratio (%).
Activity equation below calculates
Biomembrane suppression ratio (%)=(ODNegative group-ODSample)/ODNegative group×100
Active testing result is as shown in Table-1:
Table-1
From experimental result it can be seen that the suppression ratio of compound on cell membrane, only lower slightly than positive reference substance bromo-furanone when 1/8MIC, in other concentration, it is all high than positive reference substance, it is possible to effectively suppress the biomembrane of PA to synthesize, it is possible to as antibiotic synergist.
Claims (2)
1.N-phenylamide compound purposes in preparing antibiotic synergist, wherein said N-phenylamide compound structure is:This compound can suppress bacterial biof iotalm to be formed.
2. N-phenylamide compound purposes in preparing antibiotic synergist according to claim 1, it improves fungicidal effectiveness for medicine, disinfectant.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201410448729.5A CN104292127B (en) | 2014-09-02 | 2014-09-02 | Biomembranous formation is suppressed containing N-nitrobenzophenone amides compound |
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| CN201410448729.5A CN104292127B (en) | 2014-09-02 | 2014-09-02 | Biomembranous formation is suppressed containing N-nitrobenzophenone amides compound |
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| Publication Number | Publication Date |
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| CN104292127A CN104292127A (en) | 2015-01-21 |
| CN104292127B true CN104292127B (en) | 2016-06-15 |
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Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7498292B2 (en) * | 2002-08-15 | 2009-03-03 | The Research Foundation Of State University Of New York | Combinatorial libraries of autoinducer analogs, autoinducer agonists and antagonists, and methods of use thereof |
| US20080227684A1 (en) * | 2005-12-30 | 2008-09-18 | Belmares Michael P | Small Molecule Inhibitors of PDZ Interactions |
| JP2010043003A (en) * | 2006-11-28 | 2010-02-25 | Univ Of Tokyo | Amide compound and its salt, and biofilm formation inhibitor and biofilm remover each employing the same |
| CN102603553B (en) * | 2012-02-07 | 2014-07-30 | 中国人民解放军第二军医大学 | Compound with collaborative antifungal effect and application thereof in pharmaceuticals |
| WO2014055644A2 (en) * | 2012-10-02 | 2014-04-10 | New York University | Pharmaceutical compositions and treatment of genetic diseases associated with nonsense mediated rna decay |
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2014
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Non-Patent Citations (1)
| Title |
|---|
| The discovery of N-1 substituted 2-aminobenzimidazoles as zinc-dependent S. aureus biofilm inhibitors;Erick A. Lindsey等;《Medchemcomm.》;20121231;第3卷;1462–1465 * |
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| CN104292127A (en) | 2015-01-21 |
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Granted publication date: 20160615 Termination date: 20170902 |