Pillar[5]arene artificial transmembrane channel having antibacterial activity, and production method and application thereof

A technology of antibacterial activity and transmembrane channel, applied in the field of artificial transmembrane channel of column [5] aromatics and its preparation, can solve the problems of difficult to eliminate hemolytic toxicity, low antibacterial activity, low hemolytic toxicity, etc., and achieve inhibition of bacterial growth , excellent antibacterial properties, the effect of changing permeability

Active Publication Date: 2018-05-11
HENAN NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, although individual artificial transmembrane channels have shown antimicrobial activity similar to antimicrobial peptides, they all face the same problems: (1) low antibacterial activity; (2) hemolytic toxicity is difficult to eliminate
[0005] In summary, the current preparation methods for artificial transmembrane channels are lengthy, and there are few reports on methods that can efficiently prepare artificial transmembrane channels
Moreover, artificial transmembrane channels with high antibacterial activity and low hemolytic toxicity have not been reported yet.

Method used

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  • Pillar[5]arene artificial transmembrane channel having antibacterial activity, and production method and application thereof
  • Pillar[5]arene artificial transmembrane channel having antibacterial activity, and production method and application thereof
  • Pillar[5]arene artificial transmembrane channel having antibacterial activity, and production method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] (1) Column [4] Preparation of aromatic hydrocarbon [1] quinone

[0023]

[0024] Dissolve column [5] aromatic hydrocarbon (3g, 4mmol) in dichloromethane (50mL), add ceric ammonium nitrate (2.19g, 4mmol), stir at room temperature for 30min, add water for extraction, and then use anhydrous Na 2 SO 4 Dry, filter, and spin-dry the filtrate. After column chromatography (ethyl acetate: petroleum ether), 1.44 g of solid was obtained, and the yield was 50%.

[0025] 1 H NMR (DMSO-d6, 600MHz) δ: 8.22 (s, 2H), 6.84 (s, 2H), 6.83 (s, 2H), 6.79 (s, 2H), 6.78 (s, 2H), 6.54 (s, 2H), 3.71(s, 6H), 3.68(s, 6H), 3.65(s, 12H), 3.63(s, 6H), 3.55(s, 4H).HRMS: Calcd for C 43 H 44 NaO 10 [M+Na] + :743.2832.Found:743.2867.

[0026] (2) Preparation of dihydroxy column [5] arene

[0027]

[0028] The column [4] arene [1] quinone (0.5 g, 0.693 mmol) and sodium borohydride (0.13 g, 3.448 mmol) were dissolved in tetrahydrofuran and stirred at room temperature. After the reaction is complete, extract with...

Embodiment 2

[0035] Preparation of column [5] arene modified with double octapeptide side chain

[0036]

[0037] Dissolve the azide-modified octapeptide (48mg, 0.05mmol, 3equiv) in DMSO (3mL), add diynyl column [5] arene (13mg, 0.016mmol), add sodium ascorbate (1.5mg, 0.008mmol, 0.5 equiv) and CuSO 4 ·5H 2 O (0.4mg, 1.6μmol, 0.1equiv). After stirring for 12h, spin dry. The obtained crude product was separated and purified by HPLC, and finally 30 mg of white solid was obtained with a yield of 67%.

[0038] 1H NMR (DMSO-d6, 600MHz) δ: 12.55 (s, 2H), 10.76 (s, 4H), 8.87-7.96 (m, 20H), 7.61 (t, J = 6.0Hz, 4H), 7.30 (t, J=6.0Hz,4H),7.13-6.92(m,14H),6.78(d,J=6.0Hz,4H), 6.75(d,J=6.0Hz,4H), 5.29-4.97(m,9H), 4.55-3.79(m,22H),3.51(d,J=6.0Hz,8H),3.20-2.87(m,11H),2.02-1.97(m,3H),1.47-1.44(m,5H),1.24- 1.06 (m, 27H), 0.88 (m, 12H), 0.69-0.59 (m, 25H).

[0039] ESI-HRMS for C 145 H 180 N 26 O 30 [M+2H] 2+ calcd:1384.1769,found:1384.1838.

Embodiment 3

[0041] Preparation of column [5] arene modified with dipeptide side chain

[0042]

[0043] Dissolve the azide-modified decapeptide (64mg, 0.05mmol, 3equiv) in DMSO (3mL), add diynyl column [5] arene (13mg, 0.016mmol), add sodium ascorbate (1.5mg, 0.008mmol, 0.5 equiv) and CuSO 4 ·5H 2 O (0.4mg, 1.6μmol, 0.1equiv). After stirring for 12h, spin dry. The obtained crude product was separated and purified by HPLC, and finally 32 mg of white solid was obtained with a yield of 59%.

[0044] 1 H NMR(DMSO-d6,600MHz) δ: 10.76(s, 2H), 10.72(s, 2H), 10.71(s, 2H), 8.48(d, 2H), 8.38(t, 2H), 8.34-8.31( m, 4H), 8.18 (s, 2H), 8.15 (d, 4H), 8.04 (d, 2H), 7.99 (d, 2H), 7.92 (d, 2H), 7.83 (d, 2H), 7.59 (q ,6H),7.30-7.27(m,6H),7.12(s,2H),7.08(s,4H),7.02-6.99(m,8H),6.96-6.91(m,6H),6.78(d,4H) ), 6.75 (d, 4H), 5.32 (t, 2H), 5.28-5.19 (m, 4H), 5.02-4.96 (m, 4H), 4.60-4.52 (m, 6H), 4.40-4.35 (m, 2H) ),4.25-4.15(m,8H),3.80(d,4H),3.66-3.65(m,24H),3.51(d,6H),3.21-3.18(m,4H),3.09-3.07(m,4H) ), 2.93-2.86(...

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Abstract

The invention discloses a pillar[5]arene artificial transmembrane channel having an antibacterial activity, and a production method and an application thereof, and belongs to the technical field of compounds having an antibacterial activity. The structural general formula of the pillar[5]arene artificial transmembrane channel having the antibacterial activity is shown in the description. The invention also discloses the production method of the pillar[5]arene artificial transmembrane channel having the antibacterial activity, and an application of the pillar[5]arene artificial transmembrane channel in the preparation of medicines for treating or preventing bacterium induced diseases. The artificial transmembrane channel produced in the invention has an excellent antibacterial performance,so the artificial transmembrane channel can be well applied to the prevention and treatment of bacterium induced animal and plant diseases; and the produced artificial transmembrane channel has very low hemolysis toxicity, so the artificial transmembrane channel can be used as a whole-body ion channel type antibiotic candidate medicine.

Description

Technical field [0001] The invention belongs to the synthetic technical field of compounds with antibacterial activity, and specifically relates to a column [5] aromatic hydrocarbon artificial transmembrane channel with antibacterial activity, and a preparation method and application thereof. Background technique [0002] Pathogenic infectious diseases caused by bacteria, viruses, fungi, etc. pose a serious threat to human and animal health. So far, traditional antibiotics are still the first choice for the treatment of such infectious diseases. However, with the use of antibiotics, people gradually find that antibiotics are easy to remain, cause allergic reactions and pollute the environment. Especially in recent years, the rapid increase of multi-drug resistant pathogens has become a serious threat to human society, and the development of new antibacterial agents has become an urgent task. [0003] Antimicrobial peptides (AMPs) are a type of active peptides produced by biologic...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06C07K7/08C07K1/107A61K38/08A61K38/10A61P31/04
CPCA61K38/00C07K7/06C07K7/08C07K19/00
Inventor 辛鹏洋孙永慧孔慧渊蒋涛董文佩陈长坡王志莹王洁
Owner HENAN NORMAL UNIV
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