Application of indole-3-carbinol, diindolyl methane and derivatives thereof in preparation of medicaments for treating senile dementia

Abstract

The invention provides new application of indole-3-carbinol (I3C), diindolyl methane (DIM) and derivative compounds thereof in preparation of medicaments for treating senile dementia. By improving the expression of intracellular free radical resistant specific genes, the medicaments can enhance the automatic free radical clearing capacity of cells and lighten the harm of free radicals to the cells and tissues. The DIM, the I3C and the derivative compounds can effectively reduce the pathogenetic symptoms of senile dementia animal models, obviously improve the dyskinesia of SAM-P / 8 mice, obviously improve the superoxide dismutase (SOD) activity of brain tissues of the SAM-P / 8 mice, reduce the methylene dioxyamphetamine (MDA) content of brain tissues, reduce the choline esterase activity of the brain tissues and enhance the activities of Na<+>-K<+>-ATP enzyme and Ca<2+>-ATP enzyme of the brain tissues, so the DIM, the I3C and the derivative compounds can be used as candidate medicament molecules for treating the senile dementia. Meanwhile, the adopted small molecular substances are easily obtained, are low in price, stable in properties and convenient for storage and transportation, and have broad application prospect.

Description

technical field

[0001] The invention belongs to the technical field of biomedicine, and specifically relates to the application of indole-3-carbinol, diindolylmethane and derivatives thereof in the preparation of medicines for treating senile dementia. Background technique

[0002] Alzheimer's disease (AD) is a group of fatal neurodegenerative brain degenerative diseases with unknown etiology. The function is deteriorating continuously, the ability of daily living is progressively decreased, mainly intellectual impairment and various neuropsychiatric symptoms and behavioral disturbances. According to the statistics of the World Health Organization, there are at least 4 million patients with Alzheimer's disease (AD) in my country, so it is very necessary to study Alzheimer's disease (AD). Due to the lack of effectiveness and specificity of the drug effects of the new drugs reported so far, many toxic and side effects, or inconvenient use, difficult to absorb or difficult to ...

Examples

Embodiment 1

[0027] (Preparation of 5-chloroindole-3-methanol and 5,5'-dichlorodiindolylmethane)

[0028] Slowly add 0.86ml of phosphorus oxychloride to 2.9ml of dimethylformamide that has been cooled to 0°C in advance. 8.6mmol 5-chloroindole (purchased from Nanjing Ruima Fine Chemical Co., Ltd.) was dissolved in 1.0ml of dimethylformamide, and then slowly added to the aforementioned precooled phosphorus oxychloride solution, the formed suspension was at 37 °C for 60 minutes until the clear yellow solution turns into a pale yellow paste. Then 1 ml of ice water was added to the pasty mass, followed by slow addition of 10 ml of an aqueous solution containing 3.75 g of KOH. Heat this mixture to boil and then cool, filter, wash with water, and dry in air to obtain 5-chloroindole-3-acetaldehyde.

[0029] 1.0 g of 5-chloroindole-3-acetaldehyde was dissolved in 5.0 ml of methanol, and solid sodium borohydride was continuously added until excess. Then 50ml of water was added to the reactant, co...

Embodiment 2

[0032] (Preparation of 5-nitroindole-3-methanol and 5,5'-dinitrodiindolylmethane)

[0033] 5-Nitroindole can be purchased commercially (Nanjing Ruima Fine Chemical Co., Ltd.). Slowly add 0.92ml of phosphorus oxychloride to 2.9ml of dimethylformamide cooled to 0°C in advance. Dissolve 8.2mmol of 5-nitroindole in 1.0ml of dimethylformamide, then slowly add it to the aforementioned pre-cooled phosphorus oxychloride solution, and heat the formed suspension at 42°C for 90 minutes until a clear yellow solution Turned into a light yellow pasty substance. Then 1 ml of ice water was added to the pasty mass, followed by slow addition of 10 ml of an aqueous solution containing 3.75 g of KOH. Heat this mixture to boil and then cool, filter, wash with water, and dry in air to obtain 5-nitroindole-3-acetaldehyde.

[0034] 1.0 g of 5-nitroindole-3-acetaldehyde was dissolved in 5.0 ml of methanol, and solid sodium borohydride was continuously added until excess. Then 50ml of water was add...

Embodiment 3

[0037] (Preparation of 5-pentylindole-3-carbinol and 5,5'-dipentyl-diindolylmethane)

[0038] 5-Pentylindole can be purchased commercially (Nanjing Ruima Fine Chemical Co., Ltd.). Slowly add 0.82 ml of phosphorus oxychloride to 2.9 ml of dimethylformamide cooled to 0°C in advance. Dissolve 9.2mmol of 5-pentylindole in 1.0ml of dimethylformamide, then slowly add to the aforementioned pre-cooled phosphorus oxychloride solution, and heat the formed suspension at 37°C for 40-60 minutes until clear The yellow solution turned into a pale yellow paste. Then 1 ml of ice water was added to the pasty mass, followed by slow addition of 10 ml of an aqueous solution containing 3.75 g of KOH. Heat this mixture to boil and then cool, filter, wash with water, and dry in air to obtain 5-pentylindole-3-acetaldehyde.

[0039] 1.0 g of 5-pentylindole-3-acetaldehyde was dissolved in 5.0 ml of methanol, and solid sodium borohydride was continuously added until excess. Then 50ml of water was add...

technical field

[0001] The invention belongs to the technical field of biomedicine, and specifically relates to the application of indole-3-carbinol, diindolylmethane and derivatives thereof in the preparation of medicines for treating senile dementia. Background technique

[0002] Alzheimer's disease (AD) is a group of fatal neurodegenerative brain degenerative diseases with unknown etiology. The function is deteriorating continuously, the ability of daily living is progressively decreased, mainly intellectual impairment and various neuropsychiatric symptoms and behavioral disturbances. According to the statistics of the World Health Organization, there are at least 4 million patients with Alzheimer's disease (AD) in my country, so it is very necessary to study Alzheimer's disease (AD). Due to the lack of effectiveness and specificity of the drug effects of the new drugs reported so far, many toxic and side effects, or inconvenient use, difficult to absorb or difficult to ...

Examples

Embodiment 1

[0027] (Preparation of 5-chloroindole-3-methanol and 5,5'-dichlorodiindolylmethane)

[0028] Slowly add 0.86ml of phosphorus oxychloride to 2.9ml of dimethylformamide that has been cooled to 0°C in advance. 8.6mmol 5-chloroindole (purchased from Nanjing Ruima Fine Chemical Co., Ltd.) was dissolved in 1.0ml of dimethylformamide, and then slowly added to the aforementioned precooled phosphorus oxychloride solution, the formed suspension was at 37 °C for 60 minutes until the clear yellow solution turns into a pale yellow paste. Then 1 ml of ice water was added to the pasty mass, followed by slow addition of 10 ml of an aqueous solution containing 3.75 g of KOH. Heat this mixture to boil and then cool, filter, wash with water, and dry in air to obtain 5-chloroindole-3-acetaldehyde.

[0029] 1.0 g of 5-chloroindole-3-acetaldehyde was dissolved in 5.0 ml of methanol, and solid sodium borohydride was continuously added until excess. Then 50ml of water was added to the reactant, co...

Embodiment 2

[0032] (Preparation of 5-nitroindole-3-methanol and 5,5'-dinitrodiindolylmethane)

[0033] 5-Nitroindole can be purchased commercially (Nanjing Ruima Fine Chemical Co., Ltd.). Slowly add 0.92ml of phosphorus oxychloride to 2.9ml of dimethylformamide cooled to 0°C in advance. Dissolve 8.2mmol of 5-nitroindole in 1.0ml of dimethylformamide, then slowly add it to the aforementioned pre-cooled phosphorus oxychloride solution, and heat the formed suspension at 42°C for 90 minutes until a clear yellow solution Turned into a light yellow pasty substance. Then 1 ml of ice water was added to the pasty mass, followed by slow addition of 10 ml of an aqueous solution containing 3.75 g of KOH. Heat this mixture to boil and then cool, filter, wash with water, and dry in air to obtain 5-nitroindole-3-acetaldehyde.

[0034] 1.0 g of 5-nitroindole-3-acetaldehyde was dissolved in 5.0 ml of methanol, and solid sodium borohydride was continuously added until excess. Then 50ml of water was add...

Embodiment 3

[0037] (Preparation of 5-pentylindole-3-carbinol and 5,5'-dipentyl-diindolylmethane)

[0038] 5-Pentylindole can be purchased commercially (Nanjing Ruima Fine Chemical Co., Ltd.). Slowly add 0.82 ml of phosphorus oxychloride to 2.9 ml of dimethylformamide cooled to 0°C in advance. Dissolve 9.2mmol of 5-pentylindole in 1.0ml of dimethylformamide, then slowly add to the aforementioned pre-cooled phosphorus oxychloride solution, and heat the formed suspension at 37°C for 40-60 minutes until clear The yellow solution turned into a pale yellow paste. Then 1 ml of ice water was added to the pasty mass, followed by slow addition of 10 ml of an aqueous solution containing 3.75 g of KOH. Heat this mixture to boil and then cool, filter, wash with water, and dry in air to obtain 5-pentylindole-3-acetaldehyde.

[0039] 1.0 g of 5-pentylindole-3-acetaldehyde was dissolved in 5.0 ml of methanol, and solid sodium borohydride was continuously added until excess. Then 50ml of water was add...

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