Application of Perospirone and derivative thereof in preparation of antitumor drugs

A technology of perospirone and its derivatives, which is applied in the field of biomedicine and can solve the problems of low induction rate

Pending Publication Date: 2022-02-11
FUDAN UNIV SHANGHAI CANCER CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies have shown that perospirone inhibits methamphetamine or apomorphine-induced central stimulation or stereotyped behavior in mice and rats by blocking dopamine-2 receptors, and inhibits conditioned avoidance responses in rats; by bloc

Method used

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  • Application of Perospirone and derivative thereof in preparation of antitumor drugs
  • Application of Perospirone and derivative thereof in preparation of antitumor drugs
  • Application of Perospirone and derivative thereof in preparation of antitumor drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064] Embodiment 1: CCK8 colorimetric method investigates the cytotoxicity of perospirone hydrochloride

[0065] Using CCK8 colorimetric method to compare the effect of perospirone hydrochloride on human breast cancer MDA-MB-231 and MDA-MB-231LM2 cells, ovarian cancer A2780 cells, lung cancer H1299 and A549 cells, colorectal cancer HCT116 and SW480 cells, liver cancer MHCC -97L and SMMC-7721 cells, gastric cancer SGC-7901 cells, melanoma A375 cells, pancreatic cancer Panc-1 cells, leukemia HL60 cells, lymphoma MINO cells, esophageal cancer EC109 cells, thyroid cancer TPC-1 cells, nasopharyngeal carcinoma Effect of cytotoxic perospirone hydrochloride on growth inhibition of 5-8F cells, renal clear cell adenocarcinoma 786-O cells, glioma U251 cells, cervical cancer Siha cells, and prostate cancer PC-3 cells. Various cells were seeded in a 96-well plate at a density of 8000 cells / well. After 24 hours of seeding, the drugs were diluted to 0, 0.01, 0.1, 1, 10, 20, 40, 80, 160, 320...

Embodiment 2

[0069] Example 2: In vitro tumor growth inhibition experiment

[0070] see results Figure 1-21 , after 320μM perospirone hydrochloride acted on different tumor cells for 48h, the inhibition rates to tumor cells were 79.52±1.17% (breast cancer cell MDA-MB-231LM2, such as figure 1 shown), 77.24±0.24% (breast cancer cell MDA-MB-231, such as figure 2 shown), 89.35±0.83% (human colorectal cancer cell HCT116, such as Figure 6 shown), 83.40±0.28% (colon cancer SW480 cells, such as Figure 7 shown), 80.56±1.08% (human ovarian cancer A2780 cells, such as image 3 shown), 90.08±0.20% (lung adenocarcinoma cell H1299, such as Figure 5 shown), 89.42±0.54% (lung adenocarcinoma cell A549, such as Figure 4 shown), 92.12±0.25% (hepatoma cell MHCC-97L, such as Figure 8 shown), 89.82±1.07% (liver cancer cell SMMC-7721, as Figure 9 shown), 89.99±0.61% (gastric adenocarcinoma SGC-7901, such as Figure 10 shown), 74.65±0.56% (melanoma A375, such as Figure 11 shown), 83.07±1.36% (panc...

Embodiment 3

[0071] Example 3: Effect of Perospirone Hydrochloride on Tumor Growth in Nude Mice Bearing Human Breast Cancer Cell MDA-MB-231LM2 Orthotopic Transplantation

[0072] Adapt 6-8 week-old BALB / C female nude mice to the environment for about 1 week, digest MDA-MB-231 LM2 cells and A549 cells with trypsin, centrifuge at 1000rpm for 5min, add 5mL of fresh DMEM without FBS, wash once and count , adjust the concentration to 2×10 7 cells / mL, inoculated into fat pads of mice in 100 μl each. Wait for the tumor volume to grow to 1-20mm 3 After starting the drug. Each type of cell was randomly divided into 2 groups, 10 in each group, which were the perospirone hydrochloride (5 mg / kg) administration group and the solvent blank control group. Nude mice were numbered, and after the tumor was inoculated, intraperitoneal injection of perospirone hydrochloride was carried out by group, once a day, and each mouse was given 100 μL of medicine (1 mg / ml dissolved in 5% DMSO+30% PEG300+ 10% Tween...

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Abstract

The invention provides application of Perospirone or a derivative thereof and a pharmaceutical composition containing the Perospirone or the derivative thereof in preparation of drugs for preventing and/or treating tumors. The Perospirone has an obvious growth inhibition effect on various human tumor cells, and has an obvious inhibition effect on tumor growth of nude mice inoculated with human tumor cells. The compound has broad-spectrum antitumor activity, and experiments show that the compound has good inhibitory activity on breast cancer, ovarian cancer, lung cancer, colorectal cancer, liver cancer, gastric cancer, melanoma, pancreatic cancer, leukemia, lymphoma, esophageal cancer, thyroid cancer, nasopharynx cancer, kidney cancer, glioma, cervical cancer, prostatic cancer and other tumors; and it is shown that the Perospirone and the derivative thereof can become antitumor drugs.

Description

technical field [0001] The invention relates to the technical field of biomedical applications, in particular to the antitumor activity of perospirone and its derivatives and their application in the preparation of antitumor drugs. Background technique [0002] The chemical name of perospirone is N-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]butyl]-1,2-cis-cyclohexane Dicarboximide (N-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]butyl]-1,2-cis-cyclohexaned icarboximide), the English name is Perospirone, and the molecular formula is C23H30N4O2S, the molecular weight is 426.575. The compound is a white powder, readily soluble in DMSO (approximately 85 mg / mL), insoluble in water. Perospirone is an atypical or second-generation antipsychotic of the azapirone family. Perospirone can affect the epigenetic profile and DNA methylation of neural genes, and is also an inhibitor of the multidrug resistance protein Pgp. Directly or indirectly interfere with the function of Pgp. S...

Claims

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Application Information

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IPC IPC(8): C07D275/04A61P35/00A61P35/02A61P35/04
CPCC07D275/04A61P35/00A61P35/02A61P35/04
Inventor 金伟孙荷芬
Owner FUDAN UNIV SHANGHAI CANCER CENT
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