CN-121991007-A - Dehydroabietic acid-dithiocarbamic acid ester derivative and preparation method and application thereof

Abstract

The invention belongs to the technical field of biological medicines, and particularly discloses a dehydroabietic acid-dithiocarbamic acid ester derivative, and a preparation method and application thereof. The dehydroabietic acid-dithiocarbamic acid ester derivative has a compound with a structural general formula shown as a formula (I), or pharmaceutically acceptable salt, solvate or hydrate thereof. The invention discloses a dehydroabietic acid-dithiocarbamic acid ester derivative, a preparation method and application thereof, wherein the dehydroabietic acid-dithiocarbamic acid ester derivative has high anti-tumor activity, excellent selectivity and small toxic and side effects. (I)。

Inventors

• ZHOU XIAOQUN
• LI FANGYAO
• LI QIAN
• XU AIDI

Assignees

• 桂林医科大学

Dates

Publication Date

20260508

Application Date

20260128

Claims (10)

1. 1. The dehydroabietic acid-dithiocarbamic acid ester derivative is characterized in that the dehydroabietic acid-dithiocarbamic acid ester derivative has a compound with a structural general formula shown as a formula (I) or pharmaceutically acceptable salt, solvate or hydrate thereof, (I), Wherein R is selected from the following structures: 。
2. 2. A dehydroabietic acid-dithiocarbamic acid ester derivative according to claim 1, wherein said dehydroabietic acid-dithiocarbamic acid ester derivative is selected from the following structures: 。
3. 3. A process for preparing a dehydroabietic acid-dithiocarbamic acid ester derivative according to any one of claims 1 or 2, comprising the steps of: s1, adding dehydroabietic acid, epibromohydrin and alkali into a solvent for reaction, and after the reaction is finished, carrying out suction filtration and purification to obtain dehydroabietic acid glycidyl ester; S2, adding secondary amine and alkali into a solvent, dropwise adding carbon disulfide under an ice bath, and stirring for reaction to obtain a reaction solution; S3, dissolving the dehydroabietic acid glycidyl ester obtained in the S1 in a solvent used in the S2, adding the solvent into a reaction liquid obtained in the S2, stirring and refluxing for reaction, filtering, concentrating, extracting and purifying to obtain the dehydroabietic acid-dithiocarbamic acid ester derivative.
4. 4. A process according to claim 3, wherein in S1 the reaction temperature is 50-60 ℃ and the reaction time is 1-5 hours.
5. 5. A process according to claim 3, wherein in S2 the stirred reaction temperature is 25 ℃ and the reaction time is 0.5-1h.
6. 6. A process according to claim 3, wherein in S3 the stirring reflux reaction temperature is 70-80 ℃ and the stirring reflux reaction time is 1-12h.
7. 7. A pharmaceutical composition comprising the dehydroabietic acid-dithiocarbamate derivative according to any one of claims 1-2 or a pharmaceutically acceptable salt, solvate, hydrate thereof as an active ingredient, and one or more pharmaceutically acceptable carriers.
8. 8. The pharmaceutical composition of claim 7, wherein the pharmaceutically acceptable carrier is one or more of a solvent, a dispersant, a suspending aid, a surfactant, an isotonic agent, a thickener, a preservative, a solid binder, or a lubricant.
9. 9. Use of dehydroabietic acid-dithiocarbamic acid ester derivatives according to any one of claims 1-2 for the preparation of a medicament for the prevention or treatment of tumors.
10. 10. The use of claim 9, wherein the tumor comprises one of colon cancer, liver cancer, breast cancer, stomach cancer or lung cancer.

Description

Dehydroabietic acid-dithiocarbamic acid ester derivative and preparation method and application thereof Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to a dehydroabietic acid-dithiocarbamic acid ester derivative, a preparation method and application thereof. Background Cancer is one of the major diseases worldwide threatening human health, with its morbidity and mortality rising continuously. At present, surgery, radiotherapy and chemotherapy are the main means for clinically treating cancers. Among them, chemotherapy plays a role by nonselective killing of rapidly proliferating cells, but often accompanies serious toxic and side effects such as bone marrow suppression, gastrointestinal damage, etc., and tumor cells are prone to multi-drug resistance, resulting in treatment failure. Therefore, development of novel antitumor drugs with high efficiency, low toxicity and definite action mechanism has become an urgent need in the current drug development field. The natural product is an important treasury for the discovery of antitumor drugs due to the characteristics of various chemical structures, wide biological activity, multiple targets and the like. For example, paclitaxel, camptothecin derivatives, and the like have been successfully used in clinic. However, many natural active substances still face many challenges for direct pharmaceutical applications, such as poor water solubility, low bioavailability, toxic response caused by narrow therapeutic window, or vague action target, and difficulty in rational structural optimization. Therefore, by reasonably chemically modifying the potential natural product lead compound, the physicochemical property of the natural product lead compound is improved, the activity is enhanced and the toxicity is reduced, so that the natural product lead compound is a key strategy for promoting the conversion of the natural product lead compound into clinical medicines. Dehydroabietic acid (Dehydroabietic Acid, DHA) is a diterpenoid natural product separated from rosin and has a tricyclic phenanthrene framework structure. Studies show that DHA and its derivatives exhibit various biological activities such as anti-inflammatory, antibacterial and antitumor activities. In anti-tumor aspect, DHA can play a role in inducing apoptosis, inhibiting proliferation, metastasis and other ways. However, its own antitumor activity is weak, limiting its direct application. Disclosure of Invention The invention aims to provide a dehydroabietic acid-dithiocarbamic acid ester derivative, a preparation method and application thereof, and the dehydroabietic acid-dithiocarbamic acid ester derivative has high anti-tumor activity, excellent selectivity and small toxic and side effects. In order to solve the technical problems, the invention adopts the following technical scheme: A dehydroabietic acid-dithiocarbamic acid ester derivative has a compound with a structural general formula shown in a formula (I), or pharmaceutically acceptable salt, solvate or hydrate thereof, (I), Wherein R is selected from the following structures: 。 Preferably, the dehydroabietic acid-dithiocarbamic acid ester derivative is selected from the following structures: 。 the invention also provides a method for preparing the dehydroabietic acid-dithiocarbamic acid ester derivative, which comprises the following steps: s1, adding dehydroabietic acid, epibromohydrin and alkali into a solvent for reaction, and after the reaction is finished, carrying out suction filtration and purification to obtain dehydroabietic acid glycidyl ester; S2, adding secondary amine and alkali into a solvent, dropwise adding carbon disulfide under an ice bath, and stirring for reaction to obtain a reaction solution; S3, dissolving the dehydroabietic acid glycidyl ester obtained in the S1 in a solvent used in the S2, adding the solvent into a reaction liquid obtained in the S2, stirring and refluxing for reaction, filtering, concentrating, extracting and purifying to obtain the dehydroabietic acid-dithiocarbamic acid ester derivative. Preferably, in S1, the alkali is selected from one or more of triethylamine, N-diisopropylethylamine, pyridine, sodium carbonate and potassium carbonate, and the solvent is selected from one or more of acetone, acetonitrile, tetrahydrofuran and N, N-dimethylformamide. Preferably, in S1, the reaction temperature is 50-60 ℃ and the reaction time is 1-5h. Preferably, in S2, the alkali is selected from one or more of triethylamine, N-diisopropylethylamine, pyridine, sodium carbonate and potassium carbonate, and the solvent is selected from one of absolute ethyl alcohol, methanol and isopropanol. Preferably, in S2, the stirring reaction temperature is 25 ℃, and the reaction time is 0.5-1h. Preferably, in S3, the stirring reflux reaction temperature is 70-80 ℃, and the stirring reflux reaction time is 1-12h. The invention also provides a pharmaceutical composi