Diphenylmethane compound in gold brush as well as extraction and separation method and application of diphenylmethane compound

Abstract

The invention discloses a diphenylmethane compound in a gold brush as well as an extraction method and application thereof, the structure of the diphenylmethane compound is determined as a new compound by adopting 1H-NMR, 13C-NMR and two-dimensional nuclear magnetic spectrum analysis methods, and the diphenylmethane compound has the following structure: # imgabs0 #, r2 is methyl or hydroxyl; r3 is a methyl ester group, an ethyl ester group or hydrogen; r4 is hydroxyl or methyl; r5 is methyl or hydrogen; the diphenylmethane compound provided by the invention can effectively inhibit release of nitric oxide (NO) and inhibit activity of acetylcholin esterase (AChE), so that the compound provided by the invention can be used as an anti-inflammatory, antibacterial and anti-acetylcholin esterase lead compound, and a material basis and a theoretical basis are provided for developing new drugs.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine extraction and separation, and relates to five new diphenylmethane compounds, extraction methods and uses. Background Art

[0002] Lethariella cladonioides Nyl. Krog, also known as Jinshua Ba, Hongxue Cha and Luxin Xuecha, is a branched lichen body of the genus Lethariella, subgenus Chlorea, family Parmaliaceae. Lethariella cladonioides Nyl. Krog only exists in East Asia, and its distribution area in China involves six provinces and regions of Shaanxi, Gansu, Qinghai, Tibet, Yunnan and Sichuan. The distribution center is mainly in southeastern Tibet, northwestern Yunnan and western Sichuan. "Shaanxi Chinese Herbal Medicine" records that it is bitter in taste and neutral in nature, and has the functions of sedation, anti-inflammatory and pain relief; it is mainly used to treat epilepsy, schizophrenia, neurasthenia, headache and dizziness.

[0003] Lethariella cladonioides Nyl. Krog mainly includes various chemical components such as depsides, phenolic acids, aromatic esters and aldehydes, steroids, polyols and volatile oils, thus showing a wide range of pharmacological activities. Modern pharmacological research shows that Lethariella cladonioides Nyl. Krog has antioxidant, lipid-lowering, anti-tumor, anti-fatigue, antibacterial, anti-radiation and other effects.

[0004] At present, most of the chemical components isolated from Lethariella cladonioides Nyl. Krog are known, and the structural novelty is relatively low, but the extraction of diphenylmethane compounds from Lethariella cladonioides Nyl. Krog, extraction methods and uses have not been reported. Summary of the Invention

[0005] The purpose of the present invention is to provide diphenylmethane compounds.

[0006] The second purpose of the present invention is to provide an extraction method for diphenylmethane compounds.

[0007] The third purpose of the present invention is to provide uses of diphenylmethane compounds.

[0008] The fourth purpose of the present invention is to provide an extract of Lethariella cladonioides Nyl. Krog containing diphenylmethane compounds.

[0009] The fifth purpose of the present invention is to provide uses of the extract of Lethariella cladonioides Nyl. Krog.

[0010] The sixth purpose of the present invention is to provide a pharmaceutical composition containing diphenylmethane compounds.

[0011] The seventh purpose of the present invention is to provide uses of the above pharmaceutical composition.

[0012] The technical solution of the present invention is outlined as follows:

[0013] Diphenylmethane compounds, having the structure shown in formula (I):

[0014]

[0015] Wherein:

[0016] R1 is ethyl, methyl, hydrogen; R2 is methyl or hydroxyl; R3 is methyl ester group, ethyl ester group or hydrogen; R4 is hydroxyl or methyl; R5 is methyl or hydrogen.

[0017] The structure of the diphenylmethane compound is:

[0018]

[0019] The extraction method of the above compound includes the following steps:

[0020] Step 1: Using dried medicinal materials with a gold wire brush as raw materials, extract with ethanol-water, filter, combine the filtrates, concentrate under reduced pressure by heating, concentrate until there is no alcohol smell, cool to room temperature, and obtain an extract for later use;

[0021] Step 2: Dissolve the extract in Step 1 with pure water, extract with petroleum ether and dichloromethane, recover the solvent under reduced pressure, and obtain a three-part extract;

[0022] Step 3: Separate the dichloromethane extraction layer in Step 2 by silica gel column chromatography, and elute with petroleum ether, petroleum ether-ethyl acetate, ethyl acetate, and methanol in a gradient manner to obtain 14 fractions (Fr.d1-14) for later use;

[0023] Step 4: Further separate the fraction Fr.d9 in Step 3 by silica gel column chromatography, and elute with a petroleum ether-ethyl acetate gradient to obtain 3 fractions (Fr.d91, Fr.d92, Fr.d93);

[0024] Step 5: Separate the fraction Fr.d92 obtained in Step 4 by Sephadex LH-20, detect by thin-layer chromatography, and combine and concentrate according to the color development results for later use;

[0025] Step 6: Separate the concentrate obtained in Step 5 by reverse-phase silica gel column chromatography, elute with methanol-water as the mobile phase, detect by thin-layer chromatography, and combine and concentrate according to the color development results for later use;

[0026] Step 7: Separate and prepare the concentrate obtained in Step 6 by HPLC, elute with methanol-water as the mobile phase, and prepare 5 fractions (Fr.d921-Fr.d925).

[0027] Step 8: Separate and prepare the fraction Fr.d924 obtained in Step 7 by HPLC, elute with methanol-water as the mobile phase, and prepare compound I-1.

[0028] Step 9: Perform HPLC separation and preparation on the fraction Fr.d922 obtained in Step 7, elute with methanol-water as the mobile phase, and prepare Compound I-4.

[0029] Step 10: Perform HPLC separation and preparation on the fraction Fr.d923 obtained in Step 7, elute with methanol-water as the mobile phase, and prepare Compounds I-2, I-3, and I-5.

[0030] The said Step 1 is preferably: using the dried medicinal materials with a golden wire brush as raw materials, adding an ethanol solution of 95% which is 8 to 16 times the mass of the raw materials, performing ultrasonic extraction 1 to 3 times, 30 minutes each time, then adding an ethanol solution of 75% which is 8 to 16 times the mass of the raw materials, performing ultrasonic extraction 1 to 3 times, filtering, combining the filtrates, recovering ethanol under reduced pressure, and concentrating until there is no ethanol left to obtain an extract; or using the dried medicinal materials with a golden wire brush as raw materials, adding an ethanol solution of 95% or 75% which is 8 to 16 times the mass of the raw materials, performing ultrasonic extraction 1 to 3 times, filtering, combining the filtrates, recovering ethanol under reduced pressure, and concentrating until there is no ethanol left to obtain an extract; or using the dried medicinal materials with a golden wire brush as raw materials, adding an ethanol solution of 95% which is 8 to 16 times the mass of the raw materials, performing heating extraction 1 to 3 times, then adding an ethanol solution of 75% which is 8 to 16 times the mass of the raw materials, performing heating extraction 1 to 3 times, filtering, combining the filtrates, recovering ethanol under reduced pressure, and concentrating until there is no ethanol left to obtain an extract; or using the dried medicinal materials with a golden wire brush as raw materials, adding an ethanol solution of 95% or 75% which is 8 to 16 times the mass of the raw materials, performing heating reflux extraction 1 to 3 times, filtering, combining the filtrates, recovering ethanol under reduced pressure, and concentrating until there is no ethanol left to obtain an extract.

[0031] The application of the above diphenylmethane compounds in the preparation of anti-acetylcholinesterase drugs, or in the preparation of drugs for inhibiting cell release of NO.

[0032] The golden wire brush extract containing the above diphenylmethane compounds.

[0033] The application of the golden wire brush extract in the preparation of anti-acetylcholinesterase drugs, or in the preparation of drugs for inhibiting cell release of NO.

[0034] A pharmaceutical composition, characterized by comprising a diphenylmethane compound or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier and / or excipient.

[0035] The application of the above pharmaceutical composition in the preparation of anti-acetylcholinesterase drugs, or in the preparation of drugs for inhibiting cell release of NO.

[0036] Advantages of the present invention:

[0037] The diphenylmethane compounds of the present invention can effectively inhibit the release of nitric oxide (NO) and the activity of acetylcholinesterase (AChE), suggesting that the diphenylmethane compounds of the present invention can be used as lead compounds for anti-inflammatory and anti-acetylcholinesterase. Detailed implementation mode

[0038] The technical solution of the present invention will be described below in conjunction with specific embodiments. The described embodiments are only a part of the embodiments of the present invention, rather than all embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative work belong to the protection scope of the present invention.

[0039] Example 1

[0040] The extraction method of diphenylmethane compounds includes the following steps:

[0041] Step 1: Using the dried whole herb (4.0 kg) of Lethariella cladonioides Nyl. Krog as raw material, cut it into pieces, ultrasonically extract 3 times (30 min) with 14 times the amount of 95% ethanol and 75% ethanol respectively, filter, combine to obtain the filtrate, and recover the solvent under reduced pressure at 40°C - 45°C to obtain 340 g of extract.

[0042] Step 2: Take the above extract, dissolve it with pure water, extract it with equal amounts of petroleum ether and dichloromethane, and recover the solvent from the extract under reduced pressure to obtain the dichloromethane layer extract (66.7 g).

[0043] Step 3: After dissolving the dichloromethane layer extract, add 1.2 times the amount of silica gel for sample mixing, perform silica gel column chromatography separation, and use petroleum ether, petroleum ether-ethyl acetate volume ratios of 100:1, �0:1, 25:1, 10:1, 5:1, 2:1, 1:1 and ethyl acetate, methanol as eluents for gradient elution to obtain 14 fractions (Fr.d1 - Fr.d14).

[0044] Step 4: Mix 1.3 times the amount of silica gel with fraction Fr.d9, perform silica gel column chromatography separation, and use petroleum ether-ethyl acetate volume ratios of 10:, 8:1, 4:1, 2:1, 1:1 and ethyl acetate, methanol as eluents for gradient elution to obtain 3 fractions (Fr.d91, Fr.d92, Fr.d93).

[0045] Step 5: First purify Fr.d92 with Sephadex LH-20 CH2Cl2-MeOH (1:1, v / v), and then perform ODS column chromatography, using methanol-water volume ratios of 2:8, 3:7, 4:6, 5:5, 6:4, 7:3, 8:2, 9:1 and methanol as eluents for gradient elution.

[0046] Step 6: The above sample was separated and prepared by HPLC, and isocratic elution was carried out using methanol-water as the mobile phase to obtain 5 fractions (Fr.d921, Fr.d922, Fr.d923, Fr.d924, Fr.d925).

[0047] Step 7: Fr.d924 was separated and prepared by HPLC, and isocratic elution was carried out using methanol-water as the mobile phase to obtain Compound 1.

[0048] Step 8: Fr.d923 was separated and prepared by HPLC, and isocratic elution was carried out using a methanol-water volume ratio of 68:32 as the mobile phase to obtain Compounds 2, 3, and 5.

[0049] The physical and chemical properties and constants of each compound are as follows:

[0050] Compound I-1: White powder; UV (methanol) λmax (logε) 206 (3.25), 225 (2.68), 270 (2.44) nm; IR (potassium bromide) vmax 3421, 2950, 2840, 1646, 1450, 1288, 1112, 1017 cm -1 ; High-resolution mass spectrometry (cation) m / z 405.1550 [M+H] + (Calculated molecular formula is C 21 H 25 O8, 405.1549); The carbon and hydrogen NMR spectrum data are shown in Table 1.

[0051] Compound I-2: White powder; UV (methanol) λmax (logε) 221 (3.54), 269 (3.29), 303 (2.95) nm; IR (potassium bromide) vmax 3295, 2927, 2853, 1636, 1602, 1425, 1283, 1197, 1106, 1017 cm -1 ; High-resolution mass spectrometry (cation) m / z 391.13931 [M+H] + (Calculated molecular formula is C 20 H 23 O8, 391.1393); The carbon and hydrogen NMR spectrum data are shown in Table 1.

[0052] Compound I-3: White powder; UV (methanol) λmax (logε) 204 (5.06) nm; IR (potassium bromide) vmax 3396, 2949, 2837, 1651, 1440, 1417, 1204, 1113, 1023 cm -1 ; High-resolution mass spectrometry (cation) m / z 405.1547 [M+H] + (Calculated molecular formula is C21 H 25 O8, 405.1549); The data of the carbon-hydrogen spectrum are shown in Table 1.

[0053] Compound I-4: White powder; UV (methanol) λmax (logε) 203 (4.6), 268 (3.90), 304 (3.65) nm; IR (potassium bromide) vmax 3420, 2903, 2838, 1647, 1437, 1319, 1275, 1198, 1147, 1017, 951 cm -1 ; High-resolution mass spectrometry (cation) m / z 391.1396 [M+H] + (Calculated molecular formula is C 20 H 23 O8, 391.1393); The data of the carbon-hydrogen spectrum are shown in Table 2.

[0054] Compound I-5: White powder; UV (methanol) λmax (logε) 204 (4.17), 224 (3.62), 271 (3.19) nm; IR (potassium bromide) vmax 3419, 2953, 2926, 2846, 1643, 1459, 1018 cm -1 ; High-resolution mass spectrometry (cation) m / z 319.1185 [M+H] + (Calculated molecular formula is C 17 H 19 O6, 319.1182); The data of the carbon-hydrogen spectrum are shown in Table 2.

[0055] Table 1 The hydrogen spectrum and carbon spectrum data of Compounds I-1 to I-3

[0056]

[0057] Table 2 The hydrogen spectrum and carbon spectrum data of Compounds I-4 to I-5

[0058]

[0059] By means of physical and chemical constants and modern spectroscopy (MS and NMR), combined with relevant data in the literature, its structure was identified. Compounds I-1 to I-5 are new compounds not reported in the literature. As follows:

[0060]

[0061] Example 2

[0062] Step 1: Using the dried whole herb (10.0 kg) as raw material, cut it into pieces, and extract it with 10 times the amount of 95% ethanol and 75% ethanol by heating under reflux for 3 times (30 min) respectively, filter, combine the filtrates, and recover the solvent under reduced pressure at 30°C - 45°C to obtain an extract.

[0063] Steps 2 - 10 are the same as Steps 2 - 10 in Example 1 to prepare compounds I-1 - I-5.

[0064] Example 3

[0065] Activity test of diphenylmethane compounds in inhibiting the release of nitric oxide (NO) by mouse macrophage RAW 264.7

[0066] Digest RAW 264.7 cells in the logarithmic growth phase with trypsin, adjust the density of the cell suspension to 3×10 5 / mL, inoculate 100 μL per well into a 96-well plate, and culture it in an incubator at 37°C and 5% CO2 for 24 h. When the cells grow to 80% density, group and add the corresponding drug intervention. The drug concentration is 50 μM, and each group has 3 replicate wells. Culture in the incubator for 36 h. Discard the supernatant, add 100 μL of MTT solution with a final mass concentration of 0.5 mg / mL to each well, then place the 96-well plate in the incubator for 2.5 h, discard the supernatant, add 150 μL of DMSO solution to each well, shake on a shaker for 10 min, and finally measure the absorbance value at 490 nm with an enzyme-linked immunosorbent assay (ELISA) reader.

[0067] [[ID=,17]]Digest RAW 264.7 cells in the logarithmic growth phase with trypsin, adjust the density of the cell suspension to 3×10 5 / mL, inoculate 100 μL per well into a 96-well plate, and culture it in an incubator at 37°C and 5% CO2 for 24 h. When the cells grow to 80% density, group and add the corresponding drug intervention. According to the results of cell viability detection, set the concentrations of each drug within the safe concentration range without toxic effects on the cells. The cells are divided into a normal control group, an LPS group (1 μg / mL), an LPS (1 μg / mL) + drug (6.25 μM) group, an LPS (1 μg / mL) + drug (12.5 μM) group, an LPS (1 μg / mL) + drug (25 μM) group, and an LPS (1 μg / mL) + drug (50 μM) group, with 3 replicate wells in each group. After culturing for 36 h, collect the cell supernatants from each well, and measure the NO content using the Griess method according to the kit instructions.

[0068]

[0069] Table 3 Results of the inhibition of NO release by the compounds

[0070]

[0071] Example 4

[0072] Test for acetylcholinesterase (AChE) inhibitory activity of diphenylmethane compounds

[0073] Preparation of AChE solution: Dissolve it with 10 mL of PBS buffer to prepare a 0.05 U / ml AChE solution. Preparation of ATCI solution: Weigh 21.7 mg of ATCI precisely into a centrifuge tube, add 10 mL of PBS buffer solution to the centrifuge tube and dissolve it fully to prepare a 7.5 mmol / L solution. Store it in the dark at 4 °C for later use. Preparation of DTNB solution: Weigh 39.6 mg of DTNB precisely into a centrifuge tube, then add 10 mL of phosphate buffer solution to the centrifuge tube and dissolve it fully to prepare a 10 mmol / L solution (prepare it immediately before use). Preparation of compound solution: Weigh the compound precisely and dissolve it in DMSO, and dilute the compound to different concentrations with PBS buffer solution as needed. Similarly, prepare galantamine solution as a positive control. Add 140 μL of phosphate buffer solution, 20 μL of sample solution and 20 μL of AChE solution into a 96-well plate in sequence, shake it to mix evenly, and then place it in an incubator at 30 °C for 15 min. Then add 10 μL of DTNB and 10 μL of ATCI, shake it evenly and place it in an incubator at 37 °C for 30 min. Finally, use an enzyme-linked immunosorbent assay (ELISA) reader to measure the absorbance value (OD) of each well at 412 nm. Use galantamine instead of the test sample solution for the positive control, add 20 μL of PBS instead of the sample solution for the standard group, and add 40 μL of PBS instead of the test compound solution and AChE solution for the blank group. Each group of data is parallel for 3 times, and the inhibition rate is calculated according to the following formula:

[0074] Inhibition rate (%) = (ODstandard - ODsample) / (ODstandard - ODblank) × 100%

[0075] Finally, use SPSS software to calculate the half maximal inhibitory concentration (IC 50 ) value of the test solution and the positive control drug against AChE.

[0076] Table 4 Results of the inhibitory activity of compounds against AChE

[0077]

[0078] Example 5

[0079] The K-B method was used to determine the size of the inhibition zone of the isolated compounds. Pour the freshly prepared BHI medium into a petri dish, cool it to room temperature, and use a micropipette to take OD 600The Staphylococcus aureus (S. aureus) suspension with a concentration of 0.5 was added twice, 500 μL each time, to a petri dish and evenly spread to prepare a bacteria-containing petri dish. 25 μL (concentration: 128 μg / mL) of the sample was added to a blank drug sensitivity paper and evenly pasted on the bacteria-containing petri dish at equal intervals. An equal amount of Gentamycin sulfate injection was used as a positive control, and an equal amount of DMSO was used as a negative control. Each sample was operated in parallel 3 times and placed in an incubator at 37 °C for 18 h. The diameter of the inhibition zone was recorded, and the results were averaged. Based on the results of the inhibition zone (IZ), samples with an inhibition diameter greater than 6 mm were selected for the determination of the minimum inhibitory concentration (MIC). According to the method of serial dilution by half of the initial concentration, the operation method was the same as the K-B method. It was placed in an incubator at 37 °C for 18 h. The diameter of the inhibition zone was recorded, and the results were averaged.

[0080] Table 5 Results of the inhibitory activity of the compound against Staphylococcus aureus

[0081]

[0082] The anti-inflammatory drugs and acetylcholinesterase inhibitor drugs containing the compounds or compositions of the present invention can be in dosage forms suitable for oral administration or injection, etc. For example, they can be tablets, capsules, granules, injections, pills, syrups, powders, etc.

[0083] The description of the above embodiments is only used to help understand the method and its core idea of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and modifications can be made to the present invention, and these improvements and modifications are also included in the protection scope of the claims of the present invention.

Claims

1. Diphenylmethane compounds extracted and isolated from a wire brush, characterized in that It has the structure shown in formula (I): Wherein: R1 is ethyl, methyl, hydrogen, etc.; R2 is methyl or hydroxyl, etc.; R3 is methyl ester group, ethyl ester group or hydrogen, etc.; R4 is hydroxyl or methyl, etc.; R5 is methyl or hydrogen, etc.

2. The compound according to claim 1, characterized in that The structure of the said compound is:

3. The extraction method of the compound according to claim 1, characterized in that It includes the following steps: Step 1: Using the dried medicinal materials with golden wire brush as raw materials, adding ethanol-aqueous solution, extracting, filtering, combining the filtrates and recovering ethanol under reduced pressure, concentrating until there is no ethanol left, cooling to room temperature, and obtaining the extract for standby; Step 2: Dissolving the extract in Step 1 with pure water, extracting with petroleum ether and dichloromethane, recovering the solvent under reduced pressure, and obtaining the three-part extract; Step 3: Separating the dichloromethane extraction layer in Step 2 by silica gel column chromatography, eluting with petroleum ether, petroleum ether-ethyl acetate, ethyl acetate, and methanol in gradient, detecting by thin-layer chromatography, combining according to the color development results, and concentrating to dryness under reduced pressure, which can be divided into 14 fractions (Fr.d1-14) for standby; Step 4: Separating the fraction Fr.d9 in Step 3 by silica gel column chromatography again, eluting with petroleum ether-ethyl acetate, ethyl acetate, and methanol in gradient respectively, obtaining several elution parts, detecting by thin-layer chromatography, combining according to the color development results, and concentrating to dryness under reduced pressure, obtaining 3 fractions (Fr.d91, Fr.d92, Fr.d93); Step 5: Separating the fraction Fr.d92 obtained in Step 4 by Sephadex LH-20, detecting by thin-layer chromatography, combining and concentrating according to the color development results for standby; Step 6: Separating the concentrate obtained in Step 5 by reverse-phase silica gel column chromatography, eluting with methanol-water as the mobile phase, detecting by thin-layer chromatography, combining and concentrating according to the color development results for standby; Step 7: Separating and preparing the concentrate obtained in Step 6 by HPLC, eluting with methanol-water as the mobile phase, and preparing 5 fractions (Fr.d921-Fr.d925); Step 8: Separating and preparing the fraction Fr.d924 obtained in Step 7 by HPLC, eluting with methanol-water as the mobile phase, and preparing compound I-1; Step 9: Separating and preparing the fraction Fr.d922 obtained in Step 7 by HPLC, eluting with methanol-water as the mobile phase, and preparing compound I-4; Step 10: Separating and preparing the fraction Fr.d923 obtained in Step 7 by HPLC, eluting with methanol-water as the mobile phase, and preparing compounds I-2, I-3, and I-5.

4. The method according to claim 3, wherein step 1 is as follows: using the dried medicinal materials of Jin Si brush as raw materials, adding an ethanol solution of 95% which is 8 to 16 times the mass of the raw materials, performing ultrasonic extraction 1 to 3 times for 30 minutes each time, then adding an ethanol solution of 75% which is 8 to 16 times the mass of the raw materials, performing ultrasonic extraction 1 to 3 times, filtering, combining the filtrates, recovering ethanol under reduced pressure, and concentrating until there is no ethanol left to obtain an extract; or using the dried medicinal materials of Jin Si brush as raw materials, adding an ethanol solution of 95% or 75% which is 8 to 16 times the mass of the raw materials, performing ultrasonic extraction 1 to 3 times, filtering, combining the filtrates, recovering ethanol under reduced pressure, and concentrating until there is no ethanol left to obtain an extract; or using the dried medicinal materials of Jin Si brush as raw materials, adding an ethanol solution of 95% which is 8 to 16 times the mass of the raw materials, performing heating extraction 1 to 3 times, then adding an ethanol solution of 75% which is 8 to 16 times the mass of the raw materials, performing heating extraction 1 to 3 times, filtering, combining the filtrates, recovering ethanol under reduced pressure, and concentrating until there is no ethanol left to obtain an extract; or using the dried medicinal materials of Jin Si brush as raw materials, adding an ethanol solution of 95% or 75% which is 8 to 16 times the mass of the raw materials, performing heating reflux extraction 1 to 3 times, filtering, combining the filtrates, recovering ethanol under reduced pressure, and concentrating until there is no ethanol left to obtain an extract.

5. The application of the diphenylmethane compound of claim 1 or 2 in the preparation of anti-acetylcholinesterase and antibacterial drugs, or in the preparation of drugs for inhibiting the release of nitric oxide (NO) from cells.

6. The Jin Si brush extract containing the diphenylmethane compound of claim 1 or 2.

7. The application of the Jin Si brush extract of claim 6 in the preparation of anti-acetylcholinesterase and antibacterial drugs, or in the preparation of drugs for inhibiting the release of NO from cells.

8. A pharmaceutical composition, characterized in that Comprising the diphenylmethane compound of claim 1 or 2 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier and / or excipient.

9. The application of the pharmaceutical composition of claim 8 in the preparation of anti-acetylcholinesterase and antibacterial drugs, or in the preparation of drugs for inhibiting the release of NO from cells.

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