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Novel application of caffeoylquinic acid compound

A dicaffeoyl and drug technology, applied in the field of caffeoylquinic acid compounds

Inactive Publication Date: 2013-05-01
INST OF CHEM CHINESE ACAD OF SCI +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Studies on the mechanism of action of T-705 against influenza virus have shown that although T-705 itself has no inhibitory effect on influenza virus RNA polymerase activity when it is less than 100μM, its metabolite T-705RTP (T-705 -4-ribofuranosyl-5'-triphosphate, T-705-4-ribofuranosyl-5'-triphosphate) has been proved to have a strong inhibitory activity of influenza virus RNA polymerase (IC 50 =0.14μM)

Method used

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  • Novel application of caffeoylquinic acid compound
  • Novel application of caffeoylquinic acid compound
  • Novel application of caffeoylquinic acid compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064] Embodiment 1, determine caffeoylquinic acid compound and PA by NMR experiment C Interaction dissociation constant K d

[0065] The NMR experiment was completed with a Bruker AVANCE 600 spectrometer (equipped with a 5mm BBI probe and provided with a gradient in the z direction), and the experimental operation and data processing were completed using a TOPSPIN (Bruker, version 2.1) workstation. All NMR experiments were performed at 298.2K (Bruker, B3000 temperature control unit). Relaxation edited NMR spectra using [D / presaturation-90 x -(Δ-180 y -Δ) n -acquire] pulse sequence, wherein the Carr-Purcell-Meiboom-Gill (CPMG) sequence is used for spin-lock (spin-lock), and a pre-saturation pulse is used to suppress the water peak. For all relaxation editing experiments, D = 3s, P 90 (90°pulse) is set according to different samples, Δ=1.5ms, 2×n×Δ=total spin-locking time, the number of spin-locking cycles n is set according to different experiments, the number of samplin...

Embodiment 2

[0122] Embodiment 2, RNA influenza virus polymerase activity test

[0123] The RNA influenza virus polymerase activity was tested by the ApG primer extension method reported by T. Deng et al. in J. Virol. 80 (2006) 2337-2348. The specific method is as follows: in 5mM MgCl 2 , 5mM small molecules (caffeoylquinic acid compounds), 5mM dithiothreitol, 1mM adenosine triphosphate (ATP), 0.5mM uridine triphosphate (UTP), 0.5mM cytidine triphosphate (CTP), 0.1μM[ α- 32P] guanosine triphosphate (GTP 3000Ci / mmol), and 2U / μl RNasin (Promega Company) in the presence of 2.5 μL H5N1 avian virus RNA polymerase (3P) and 0.7 μM template virus RNA promoter (equal molar 5′- A mixture of end vRNA 5′-AGUAGAAACAAGGCC-3′ and 3′-endvRNA 5′-GGCCUGCUUUUGCU-3′) was performed in a 5 μL reaction. 0.5mM ApG primer sequence (Sigma company) was added to the reaction system and incubated at 30°C for 1 hour. After adding 5 μL of 2× formamide / bromophenol blue / EDTA loading buffer, the mixture was heated at 9...

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Abstract

The invention discloses a novel application of a caffeoylquinic acid compound. The novel application of caffeoylquinic acid compound provided in the invention shown in a formula I is an application of being as an influenza virus RNA polymerase inhibitor on one hand; on the other hand, the novel application of caffeoylquinic acid compound is an application of preparing the medicament for preventing and / or treating the diseases relative to the influenza virus RNA polymerase, especially relates to an application of preparing the medicament in resisting influenza virus, more especially relates toan application of preparing the medicament in resisting bird flu virus (H5N1).

Description

technical field [0001] The invention relates to a new application of caffeoylquinic acid compounds. Background technique [0002] The highly pathogenic avian influenza virus (H5N1) originating from birds is a serious threat to human health. Since Hong Kong reported the first case of avian influenza transmitted from chickens to humans in 1997, the virus has broken out on a large scale in Southeast Asia and spread rapidly to many countries and regions. Avian influenza virus replicates rapidly and mutates frequently, and can be transmitted from birds to humans, causing severe respiratory diseases and high morbidity and mortality in infected persons. [0003] Anti-avian influenza drugs are mainly divided into three categories according to their targets: [0004] (1) Neuraminidase inhibitors [0005] Viral hemagglutinin (H) is required for the binding of influenza virus to receptors carrying N-acetylneuraminic acid (NANA, sialic acid). Viral neuraminidase (N) then cleaves N-a...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/216A61P31/16
Inventor 李林常圣海向俊锋梁欢欢李骞唐亚林刘迎芳
Owner INST OF CHEM CHINESE ACAD OF SCI
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