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A class of diterpenoid derivatives with mdr reversal activity and their applications

A technology of saffron and derivatives, applied in the field of saffron diterpene derivatives, can solve the problems of insignificant reversal effect and the like

Active Publication Date: 2022-07-15
CHENGDU INST OF BIOLOGY CHINESE ACAD OF S
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the published euphorbia factor and its derivatives, the reversal effect is not significant

Method used

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  • A class of diterpenoid derivatives with mdr reversal activity and their applications
  • A class of diterpenoid derivatives with mdr reversal activity and their applications
  • A class of diterpenoid derivatives with mdr reversal activity and their applications

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0098] Example 1: Preparation and determination of compounds 1-41

[0099] 1. Preparation of compounds 1, 37 and 40. In a 1% (m / v) NaOH / MeOH solution system, compounds 18, 38, and 39 were used as raw materials (compound 18 corresponds to compound 1, and so on), and the reaction was carried out at room temperature for 24 hours. After the reaction, it was extracted with ethyl acetate, concentrated, and separated by a chromatographic column (elution with a mixed solution of petroleum ether and ethyl acetate) to obtain the target product. The NMR data of compounds 1, 37, and 40 are shown below, respectively.

[0100] Compound 1: HRMS-ESI-TOF: [M+Na]+373; mp 226-228°C; 1 H NMR(400MHz, Acetone)δ7.29(d,J=11.6Hz,1H,H-12),5.07(s,1H,H-17α),4.96(d,J=8.5Hz,1H,H-7 ), 4.81(s, 1H, 17β), 4.68(s, 1H, OH-15), 4.44(s, 1H, H-5), 4.37(s, 1H, H-3), 4.32(s, 2H, OH-5, OH-7), 4.06 (s, 1H, OH-3), 3.07 (dd, J=13.2, 8.8Hz, 1H, H-1α), 2.21 (dd, J=8.4, 3.3Hz, 1H , H-4), 1.96–1.85 (m, 2H, H-2, H-8α), 1...

Embodiment 2

[0155] Example 2: In vitro activity test of compounds 1-41

[0156]1. Cytotoxicity detection of diterpene derivatives of Radix Glycyrrhizae. Specific operation: MCF-7 and MCF-7 / ADR cells were seeded in a 96-well plate according to the limited number of 1×110 cells / well, and 100 μL of MEM medium containing 10% fetal bovine serum was added to each well and cultured for 15 hours until the cells grew. To cover 70% of the pore area, compounds Nos. 1 to 41 with a final concentration gradient of 1 μM, 5 μM, 20 μM, 50 μM, and 100 μM were added successively. All compounds were dissolved in DMSO, and the administration volume was 1 μL. Doxorubicin with a final concentration gradient of 0.01 μM, 0.1 μM, 1 μM, 5 μM, and 10 μM was set as a positive control, the compound was dissolved in DMSO, and the administration volume was 1 μL. DMSO was set as a negative control, and the administration volume was 1 μL. Set 3 wells in each group as parallel samples. After culturing at 37°C for 48 hou...

Embodiment 3

[0167] Example 3: Intracellular aggregation experiment

[0168] This example provides compounds 8 and 31 for the detection of intracellular aggregation of rhodamine 123 (Rh123). Specific operation: MCF-7 / ADR and MCF-7 cells were divided into 2 × 10 6 The density of cells / well was inoculated into a 24-well plate, incubated at 37°C for 16 h, and pretreated with compound 8 and compound 31 (concentrations of 2, 10 and 20 μM, respectively) for reversal of drug resistance for 1 h, and the final concentration was 20 μM. verapamil was used as a positive control. The cells were then incubated with Rh123 at a final concentration of 5 μM for 1 h at 37°C in the dark. Cells were washed twice with PBS, resuspended in PBS buffer, and analyzed by flow cytometry. The experimental results are as figure 1 , as shown in Table 3. figure 1 It is a schematic diagram showing the changes of rhodamine accumulation in MCF-7 / ADR cells of compound 8 and compound 31, respectively.

[0169] Table 3 Co...

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Abstract

The invention belongs to the field of organic chemistry, and in particular relates to a class of diterpenoid derivatives with MDR reversal activity and applications thereof. The present invention extracts new diterpenoid derivatives from Euphorbia spp Meter. Among them, the reversal multiple of compound 17 was as high as 460.32.

Description

technical field [0001] The invention belongs to the field of organic chemistry, and in particular relates to a class of diterpenoid derivatives with MDR reversal activity and applications thereof. Background technique [0002] Multidrug resistance (MDR) refers to the phenomenon of resistance to one drug, accompanied by resistance to other drugs that have nothing to do with structure and function; MDR is one of the main reasons for the failure of chemotherapy in malignant tumors. One of the main mechanisms leading to the occurrence of MDR is the overexpression of P-gp. As an energy-dependent efflux pump, P-gp can reduce the accumulation of anticancer drugs in cells, thereby reducing the efficacy of drugs. Therefore, compounds capable of inhibiting P-gp activity may have the potential to reverse MDR. [0003] Among the many compounds, Euphorbia factor L 1 -L 11 It was found to have antitumor, antiviral, anti-inflammatory and other activities, and was regarded as the most p...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C49/743C07C49/753C07C205/57C07C69/33C07C69/612C07C69/618C07C69/78C07C69/76C07D493/10C07D303/06A61P35/00
CPCC07C49/743C07C49/753C07C205/57C07C69/33C07C69/612C07C69/618C07C69/78C07C69/76C07D493/10C07D303/06A61P35/00C07B2200/07C07C2603/38
Inventor 焦威向玲邵华武王飞张中辉
Owner CHENGDU INST OF BIOLOGY CHINESE ACAD OF S
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