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Application of amantadine-gardenia amide A heterozygote compound in drug for treating Parkinson's disease

A technology of gardeniamide and amantadine, which is applied in the field of medicine, can solve problems such as drug side effects, and achieve high safety, safe and effective neuroprotective effect, and strong neuroprotective effect

Active Publication Date: 2018-03-23
广州药本君安医药科技股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these drugs have different degrees of side effects, and some of them have gradually withdrawn from clinical application.

Method used

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  • Application of amantadine-gardenia amide A heterozygote compound in drug for treating Parkinson's disease
  • Application of amantadine-gardenia amide A heterozygote compound in drug for treating Parkinson's disease
  • Application of amantadine-gardenia amide A heterozygote compound in drug for treating Parkinson's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Cytotoxicity of compound F1 against normal SH-SY5Y.

[0037] Experimental material: human neuroblastoma cell line SH-SY5Y, purchased from the Cell Bank of the Chinese Academy of Sciences in Shanghai

[0038] Experimental procedure: Digest SH-SY5Y cells in the logarithmic phase, centrifuge, resuspend the cells in complete medium containing 10% fetal bovine serum FBS, and inoculate 5×10 3 The SH-SY5Y cells per well were placed in a 96-well plate, and the volume of the cell suspension in each well was 100 μL. Four concentrations of 10 and 100 μM, each with 8 replicate wells, were cultured in a constant temperature incubator for 24 hours. After adding different concentrations of medicinal solutions for pretreatment for 3 hours, discard the old medicinal solutions, wash once with PBS, add 25 μL of MTT with a concentration of 5 mg / mL to each well, and after incubation for 3 hours, absorb the MTT solution, add 150 μL of fresh DMSO to each well, Shake for 10 min, and use an e...

Embodiment 2

[0042] Detection of F1 to MPP by CCK8 method + Influence of damaged SH-SY5Y cell viability.

[0043] Experimental procedure: Set blank group, control group, ATD group, GA group, ATD+GA group and F1 group in a 96-well plate, and set seven concentrations of 2.5, 5, 10, 20, 40, 80 and 160 μM in each group, and add 2mM modeling drug MPP + Processing 24h. Add 10 μL of CCK8 solution directly to each well, and finally place it in a microplate reader for measurement at a wavelength of 450 nm, and calculate the inhibition rate.

[0044] According to the experimental results, take the logarithm value of the sample concentration as the abscissa, and the inhibition rate as the ordinate, draw the inhibition curve, and calculate the half-maximum effect concentration EC of different samples according to the curve 50 . See the experimental results figure 2 , indicating that F1 and its prodrugs have an effect on MPP + Injured SH-SY5Y cells have a certain degree of neuroprotection, EC 5...

Embodiment 3

[0047] Examining F1 vs. MPP + Effects on morphology of injured SH-SY5Y cells.

[0048] According to the steps in Example 2, the normal cells and the drug-treated cells were observed under the same microscope and the same lens, and the morphology of the cells was recorded.

[0049] See the experimental results Figure 4 . The results showed that normal SH-SY5Y cells were larger in volume, smaller in gaps, and full-bodied in polysynaptic shape. When it is subject to MPP + After injury, the number of cells decreased and the morphology was long spindle. When pre-administered 20 μM F1 to protect cells, compared with the model group, the cell morphology and cell density were significantly improved; while the cell morphology of the ATD group had no significant change, and both the GA and ATD+GA groups had a certain degree of protection. The results showed that the neuroprotective effect of F1 was better than that of its prodrug and its combined drugs.

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Abstract

The invention discloses an application of an amantadine-gardenia amide A heterozygote compound in a drug for treating Parkinson's disease, and a structure of the compound is as shown in formula I. Thecompound can increase a DA level in a Parkinson's cell model, can inhibit the synthesis of an NMDA receptor by inhibiting the protein expression of NR1, thereby inhibiting the internal flow of extracellular Ca<2+>, so that the activity and protein level of i-NOS can be decreased, the NO is significantly decreased, the necrocytosis is reduced, the nerve cell apoptosis can be resisted, and an effect for protecting the nerves can be realized. Being applied to a mice Parkinson's model, the compound can improve dyskinesia of mice. The compound of the invention can be used as a DA control agent, aniNOS control agent and an NMDA receptor antagonist; and the compound can be applied to the drug for treating Parkinson's diseases, particularly for treating behavior disorder and diseases caused by neuronal apoptosis.

Description

technical field [0001] The invention belongs to the field of medicines, and in particular relates to the application of amantadine-gardeninamide A hybrid compound in the treatment of Parkinson's disease. Background technique [0002] Parkinson's Disease (PD), also known as Parkinson's palsy, is a neurodegenerative disease that seriously endangers the quality of life and health of patients. It is common and difficult to cure in clinical practice. The incidence of PD is very high, up to 0.3% in the general population. The main pathological changes of the disease are the damage of dopaminergic neurons in the nigrostriatal pathway and the appearance of Lewy bodies in neuronal cell bodies. The main clinical features are tremor paralysis, stiffness, bradykinesia, poor motor autonomy, etc., which seriously affect the quality of life of patients. Therefore, the drug treatment of Parkinson's disease has always been an important area of ​​concern for drug developers. [0003] The p...

Claims

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Application Information

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IPC IPC(8): A61K31/435C07D221/04A61P25/16
CPCA61K31/435C07D221/04
Inventor 陈河如彭丽芝李艳冰张潮李怡芳何蓉蓉张磊
Owner 广州药本君安医药科技股份有限公司
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