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Application of compound in preparation of drug used for resisting Schistosomiasis japonicum

A technology for schistosomiasis and compounds, applied in the field of medicine, can solve problems such as no public reports yet

Active Publication Date: 2014-03-12
STATION OF VIRUS PREVENTION & CONTROL CHINA DISEASES PREVENTION & CONTROL CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] At present, there is no public report involving the compound of structural formula (I) for anti-schistosomiasis japonicum

Method used

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  • Application of compound in preparation of drug used for resisting Schistosomiasis japonicum
  • Application of compound in preparation of drug used for resisting Schistosomiasis japonicum
  • Application of compound in preparation of drug used for resisting Schistosomiasis japonicum

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1. Homology modeling of the tertiary structure of SjOAR protein

[0031] The homology modeling of the tertiary structure of the SjOAR protein was completed using the template-based structure prediction server HHpred, followed by Modeller for model construction. The template with the highest homology is an enone reductase (PDB ID: 1IY8) from Corynebacterium aquaticus M-13, which belongs to the short-chain dehydrogenase family, and its structure binds NADH and inhibitor 2 -Presented in the form of a methyl-2,4-pentanediol complex, the conserved region for NADH binding and the conserved site for inhibitor binding provide an ideal binding region for molecular docking (see figure 1 ). The predicted structure of SjOAR shows that the protein is composed of 6 α-helices and 6 β-sheets, presenting an α / β "sandwich" structure as a whole, with α-helices on both sides and β-sheets in the middle, parallel to each other. A typical Rossmann-fold structure is formed. The pre...

Embodiment 2

[0032] Example 2. Virtual Screening

[0033] Candidate molecules: 14,400 small molecule compounds included in Maybridge HitFinder.

[0034] Screening principles: Follow the Lipinski principle, that is, the compound has no more than 5 hydrogen bond donors, no more than 10 hydrogen bond acceptors, a molecular weight of no more than 500Da, and a logP value of n-octanol-water partition coefficient less than 5.

[0035] Screening method: 14,400 small molecules were scored by docking with SjOAR protein using the Sybyl v8.0 Surflex docking program (www.tripos.com), and the compounds whose scoring function was in the top 5% were identified, and the software AutoDock4 was used again .2 Perform docking scoring verification (http: / / autodock.scripps.edu / ). Finally, the small molecules whose scoring function was in the top 27 were determined for the in vitro insecticidal activity test (Table 1 below). figure 2 It is the molecular docking result of compound OAR27 and SjOAR protein.

[0...

Embodiment 3

[0038] Example 3. In vitro screening of active compounds against Schistosoma japonicum

[0039] 1. Experimental materials and methods

[0040] 1. Parasites

[0041] The cercariae of Schistosoma japonicum (Anhui strain) were provided by China CDC Center for Parasitic Disease Prevention and Control.

[0042] 2. Host

[0043] Kunming rats, weighing between 18-22 g, were purchased from Shanghai Experimental Animal Center, Chinese Academy of Sciences.

[0044] 3. Inoculation of animals and collection of worms

[0045] Vaccination: by the method of abdominal infection. The mice were fixed on a wooden board with rubber bands, and then their abdominal hair was shaved off with an elevator, and each mouse was infected with 80-100 cercariae.

[0046] Harvesting worms: Mice infected with cercariae for 35 days were sacrificed by cutting the carotid artery and exsanguinating blood, and then perfusing the thoracic artery with ice-cold normal saline supplemented with sodium heparin to co...

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Abstract

The invention discloses application of a compound with a structural formula (I) in preparation of a drug used for resisting Schistosomiasis japonicum. According to the invention, through deep analysis of the synthetic route of aliphatic acid of Schistosomiasis japonicum, it is believed 3-oxoacyl-ACP reductase (OAR) participating in the synthetic route is a crucial rate-limiting enzyme; on such a basis, target screening of compounds and in vitro insecticidal activity tests are carried out, then inhibition of the selected compound with insecticidal activity on the activity of target protein OAR is analyzed, and finally, toxicity of the active compound on a host cell is assessed. The compound with the structural formula (I) has substantial insecticidal activity and the potential of becoming a lead compound for resistance of Schistosomiasis japonicum and provides a novel approach and means for treatment of Schistosomiasis japonicum.

Description

technical field [0001] The invention belongs to the field of medicine and relates to the medical application of a compound, in particular to the application of a compound in the preparation of anti-schistosomiasis japonica medicine. Background technique [0002] Schistosomiasis is an important long-neglected tropical parasitic disease after malaria. It is estimated that about 779 million people in 76 countries or regions in the world are threatened by schistosomiasis, and the number of people infected with schistosomiasis has exceeded 200 million [Steinmann P, Keiser J, Bos R, Tanner M, Utzinger J (2006) Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk. Lancet Infect Dis 6:411-425.; Lammie PJ, Fenwick A, Utzinger J (2006) A blueprint for success: integration of neglected tropical disease control programmes. Trends Parasitol 22:313-321.]. There are mainly three kinds of schistosomiasis pathogens that endanger...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/655A61P33/12
CPCY02A50/30
Inventor 胡薇刘建王吉鹏王树奇杨忠徐斌鞠川
Owner STATION OF VIRUS PREVENTION & CONTROL CHINA DISEASES PREVENTION & CONTROL CENT
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