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AMPK (Adenosine Monophosphate Activated Protein Kinase) activating agent and application thereof in preparation of medicaments for treating diabetes mellitus and/or diabetic complication

A technology for diabetes and complications, used in drug combinations, urinary system diseases, sexual diseases, etc.

Active Publication Date: 2015-01-14
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But so far, no research has shown that HSD and other 3H-1,2-dithiol-3-thione compounds have the pharmacological activity of activating AMPK and their role in the treatment and / or prevention of diabetes and its complications

Method used

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  • AMPK (Adenosine Monophosphate Activated Protein Kinase) activating agent and application thereof in preparation of medicaments for treating diabetes mellitus and/or diabetic complication
  • AMPK (Adenosine Monophosphate Activated Protein Kinase) activating agent and application thereof in preparation of medicaments for treating diabetes mellitus and/or diabetic complication
  • AMPK (Adenosine Monophosphate Activated Protein Kinase) activating agent and application thereof in preparation of medicaments for treating diabetes mellitus and/or diabetic complication

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0079] The compound shown in embodiment 1 formula I is to the activation of macrophage cell AMPK

[0080] Take out the mouse macrophage cells from the liquid nitrogen tank and quickly place them in warm water at 37°C to shake gently to thaw, centrifuge at 1000 rpm for 3 minutes, discard the supernatant, and culture the cells in DMEM with a mass fraction of FBS of 10%. When the coverage rate of the cells in the culture dish reached 60%-70%, subculture was carried out. After the subcultured cell coverage reached 60%-70%, the cells were obtained by centrifugation at 1000 rpm for 3 min, stained with trypan blue, and counted under a microscope with a hemocytometer. Dilute the counted cells to a concentration of 150,000 / mL~200,000 / mL, and spread on a 96-well plate at a concentration of 15,000 / well to 20,000 / well.

[0081] Prepare a 3H-1,2-dithiocyclopentene-3-thione compound solution, weigh the compound shown in formula I, and dissolve it in DMSO so that the final concentration of ...

Embodiment 2

[0088] Example 2 The activating effect of the compound represented by formula I on macrophage AMPK under LPS-induced inflammation conditions

[0089] Take the mouse macrophage cells out of the liquid nitrogen tank and quickly place them in warm water at 37°C and shake gently to thaw, centrifuge at 1000 rpm for 3 minutes, discard the supernatant, and place the cells in DMEM medium with a mass fraction of FBS of 10%. Cultivate and subculture when the cell coverage in the culture dish reaches 60%-70%. After the subcultured cell coverage reached 60%-70%, the cells were obtained by centrifugation at 1000 rpm for 3 min, stained with trypan blue, and counted under a microscope with a hemocytometer. Dilute the counted cells to a concentration of 150,000 / mL~200,000 / mL, and spread on a 96-well plate at a concentration of 15,000 / well to 20,000 / well.

[0090] Prepare a 3H-1,2-dithiocyclopentene-3-thione compound solution, weigh the compound shown in formula I, and dissolve it in DMSO so ...

Embodiment 3

[0099] The activation effect of the compound shown in Example 3 formula I on human cell KEK293T AMPK

[0100] Take the KEK293T cells out of the liquid nitrogen tank and quickly place them in warm water at 37°C to shake gently to thaw, centrifuge at 1000 rpm for 3 minutes, discard the supernatant, and culture the cells in DMEM medium with a mass fraction of FBS of 10%. Subculture was carried out when the coverage rate in the petri dish reached 60%-70%. After the subcultured cell coverage reaches 60%-70%, centrifuge at 1000 rpm for 3 minutes to obtain the cells, stain with trypan blue, count 150,000 / mL~200,000 / mL under a microscope with a hemocytometer, and spread on a 96-well plate , 15,000 / hole to 20,000 / hole.

[0101] Prepare a 3H-1,2-dithiocyclopentene-3-thione compound solution, weigh the compound shown in formula I, and dissolve it in DMSO so that the final concentration of the solution is 50 mmol / L in terms of mass concentration.

[0102]

[0103] Formula I

[0104]...

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Abstract

The present invention relates to the field of drugs, and more particularly to an AMPK activator and an application thereof in preparing drugs for treating and / or preventing diabetes and / or diabetes complications. The present invention provides an application of a 3H-1,2-disulfoheterocyclic pentene-3-thione compound having the structure of the formula (I) as an AMPK activator, and an application of the 3H-1,2-disulfoheterocyclic pentene-3-thione compound in preparing drugs for treating and / or preventing diabetes and / or diabetes complications. Because such compounds do not contain biguanide group, during the use of the compound as an AMPK activator, the compound does not cause lactic acidosis, and prepared drugs for treating and / or preventing diabetes and / or diabetes complications are safer.

Description

technical field [0001] The invention relates to the field of medicines, in particular to an AMPK activator and its application in the preparation of medicines for treating and / or preventing diabetes and / or diabetic complications. Background technique [0002] Diabetes is a disease process of multiple etiologies that affects 6% of the global population. It is estimated that by 2025, the number of patients will double to 300 million. The most important clinicopathological feature of diabetes is increased plasma glucose (blood sugar) concentration. Increased blood sugar concentration is the main cause of various clinical symptoms of diabetes. Uncontrolled hyperglycemia leads to many diabetic complications, such as increased risk of microvascular and macrovascular diseases, including nephropathy, neuropathy, retinopathy, hypertension, cerebral ischemia and coronary heart disease. Therefore, lowering blood sugar is the key to the treatment and prevention of diabetes and its co...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/385A61K31/4436A61P3/10A61P9/12A61P9/00A61P3/04A61P25/00A61P9/10A61P13/12A61P15/00
CPCA61K31/385A61K31/4436A61P3/04A61P3/10A61P9/00A61P9/10A61P9/12A61P13/12A61P15/00A61P25/00
Inventor 程坚敖桂珍贾佳
Owner SUZHOU UNIV
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