Hesperetin derivative containing thiosemicarbazone structure and application thereof
By developing hesperidin derivatives containing a thiourea structure, the problem of insufficient efficacy of existing antioxidants and α-glucosidase inhibitors has been solved, achieving significant antioxidant and inhibitory effects, with IC50 values significantly superior to traditional drugs.
Patent Information
- Application Number
- CN202511587833.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-11-03
- Publication Date
- 2026-02-06
AI Technical Summary
Existing antioxidants and alpha-glucosidase inhibitors are insufficient in terms of efficacy and side effects, making it difficult to meet clinical needs.
A hesperidin derivative containing a thiourea structure was developed, with the specific compound molecular formula C18H19N3O5S. It exhibits significant antioxidant and α-glucosidase inhibitory activities, and its IC50 value is superior to that of traditional agents, as verified by experiments.
This compound has antioxidant capacity comparable to vitamin C, with an IC50 value of 6.17 μg/mL for scavenging DPPH, which is 200 times better than vitamin E; and an IC50 value of 4.53 μg/mL for inhibiting α-glucosidase, which is 51 times better than acarbose.
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Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of medicine, in particular to a hesperetin derivative containing a thiosemicarbazone structure, and also relates to the application of the hesperetin derivative containing the thiosemicarbazone structure in antioxidation and anti-alpha-glucosidase. BACKGROUND
[0002] Free radicals are associated with the progression of a variety of health conditions in humans, such as cancer, heart disease, neurodegenerative diseases, Alzheimer's disease, etc. The human body is equipped with a complex antioxidant defense system that can effectively counteract the harmful effects of free radicals. Numerous studies have shown that antioxidants can improve overall health by slowing down or preventing the development of degenerative diseases and age-related diseases. Therefore, developing new antioxidants with higher efficacy and fewer side effects is an important research direction in the field of medicinal chemistry.
[0003] Diabetes, especially type II diabetes, has become a global epidemic, affecting more than 350 million people worldwide and is considered an important factor leading to death. Alpha-glucosidase inhibitors are an important class of drugs for the treatment of type II diabetes. Common alpha-glucosidase inhibitors, such as acarbose, miglitol and voglibose, are widely used in clinical practice to delay carbohydrate digestion, thereby reducing postprandial blood glucose peaks and improving glycemic control. Therefore, developing new alpha-glucosidase inhibitors with higher efficacy and fewer side effects is a continuing research direction in the field of medicinal chemistry. SUMMARY
[0004] The present application aims to provide a hesperetin derivative containing a thiosemicarbazone structure with good antioxidant and anti-alpha-glucosidase activity.
[0005] The present application relates to a thiochromanone derivative containing a thiosemicarbazone structure, the compound has a molecular formula of C 18 H 19 N3O5S, and has the following structural formula:
[0006]
[0007] The present application relates to the application of a thiochromanone derivative containing a thiosemicarbazone structure in antioxidation, the compound has an IC 50 value of 6.17 μg / mL, which is comparable to the activity of the control drug vitamin C, the IC 50 value of the activity of the control drug vitamin C is 6.38 μg / mL; the IC 50 value of the activity of the control drug vitamin E is 0.04 μg / mL, which is 200 times higher than the activity of the control drug vitamin E, the IC 50The value is 8.04 pg / mL.
[0008] A class of thiochromanone derivatives containing a thiosemicarbazone structure for inhibiting alpha-glucosidase, the IC 50 The value is 4.53 pg / mL, which is 51 times higher than that of the control drug acarbose, and the IC 50 The value is 237.48 pg / mL. DETAILED DESCRIPTION
[0009] Experimental Example 1: Determination of the DPPH and ABTS scavenging activity of the compound
[0010] DPPH scavenging activity determination: 5 mg of the compound was dissolved in 100 mL of methanol to prepare a stock solution with a concentration of 50 pg / mL; then 160 pL of the stock solution and 40 pL of a DPPH solution with a concentration of 0.5 pM were added to a 96-well plate to obtain a reaction mixture with a concentration of 40 pg / mL, which was reacted in the dark for 30 min, and then its absorbance value was measured at 517 nm using a full-wavelength multifunctional enzyme marker, with dimethyl sulfoxide as the negative control and vitamin C as the positive control.
[0011] ABTS scavenging activity determination: 0.2 mL of a K2S2O8 solution with a concentration of 2.6 mM was mixed with 0.2 mL of an ABTS solution with a concentration of 7.4 mM, which was diluted 50 times with a PBS buffer with a pH of 7.4 and used after being reacted in the dark at room temperature for 12 h; then 6.25 mg of the compound was dissolved in 100 mL of methanol to obtain a stock solution with a concentration of 62.5 pg / mL, and then 160 pL of the stock solution and 40 pL of the ABTS solution were added to a 96-well plate to obtain a reaction mixture with a concentration of 50 pg / mL, which was reacted in the dark for 30 min, and then its absorbance value was measured at 734 nm using a full-wavelength multifunctional enzyme marker, with dimethyl sulfoxide as the negative control and vitamin E as the positive control.
[0012] The calculation formula for the DPPH and ABTS scavenging activity of the compound is as follows:
[0013] Scavenging activity (%) = (OD value of the control group - OD value of the treatment group) / OD value of the control group x 100%;
[0014] The scavenging activity and IC 50 value of the compound were determined according to the above method, and the results are shown in Table 1.
[0015] Table 1 Scavenging activity of the compound on DPPH and ABTS
[0016]
[0017] From Table 1, it can be seen that the IC 50 value of the compound for DPPH scavenging activity is 6.17 μg / mL, which is equivalent to the activity of the control drug vitamin C; the IC 50 value for ABTS scavenging activity is 0.04 μg / mL, which is 200 times higher than the activity of the control drug vitamin E.
[0018] Experimental Example 2: Determination of the α-glucosidase inhibitory activity of the compound
[0019] 4 mg of the compound was dissolved in 100 μL of dimethyl sulfoxide and 900 μL of PBS buffer at pH 6.8 to prepare a stock solution at a concentration of 400 μg / mL, and then 20 μL of α-glucosidase at a final concentration of 0.5 U / mL, 70 μL of PBS buffer, 80 μL of a sodium carbonate solution at a concentration of 0.2 M and 10 μL of the test compound stock solution were sequentially added to a 96-well plate; after 10 min of reaction at 37°C, 20 μL of p-nitrophenyl-β-D-glucopyranoside at a final concentration of 2.5 mM was added, and after 30 min of reaction at 37°C, the absorbance was measured at 405 nm using a full-wavelength multifunctional microplate reader, with dimethyl sulfoxide as the negative control and acarbose as the positive control.
[0020] The formula for calculating the α-glucosidase inhibitory activity of the compound is as follows:
[0021] α-glucosidase inhibitory activity (%) = (OD value of the control group - OD value of the treatment group) / OD value of the control group x 100%;
[0022] The inhibitory activity and IC 50 value of the compound were determined according to the above method, and the results are shown in Table 2.
[0023] Table 2: α-glucosidase inhibitory activity of the compound
[0024]
[0025] From Table 2, it can be seen that the IC 50 value of the compound for α-glucosidase inhibitory activity is 4.53 μg / mL, which is 51 times higher than the activity of the control drug acarbose.
Claims
1. The present invention discloses a hesperetin derivative containing a thiosemicarbazone structure, characterized in that The molecular formula of the compound is C 18 H 19 N3O5S, having the following structural formula:
2. Use of a hesperetin derivative containing a thiohydantoin structure for the inhibition of α-glucosidase.
3. Use of a hesperetin derivative containing a thiohydantoin structure for the DPPH and ABTS scavenging activity.