Novel podophyllotoxin spliced anti-tumor active molecular compound as well as preparation method and application thereof

Abstract

The invention discloses a novel podophyllotoxin spliced antitumor active molecular compound which is prepared by the following steps: reacting podophyllotoxin with succinic anhydride in an organic solvent under the catalysis of a catalyst organic alkaline small molecule and the action of an acid-binding agent to generate an intermediate; and then, respectively putting anti-tumor active molecules and the intermediate into an organic solvent, and carrying out esterification reaction under the catalysis of a catalyst organic alkaline small molecule and the action of a condensing agent to obtain the novel podophyllotoxin spliced anti-tumor active molecule compound. The compound has an important application value on drug screening and pharmaceutical industry, in-vitro antitumor activity screening finds that the compound has a very good inhibition effect on human non-small cell lung cancer cells and human lung adenocarcinoma cis-platinum-resistant strains, the cytotoxicity of the compound on the human lung adenocarcinoma cis-platinum-resistant strains is more than 80 times that of a positive control drug etoposide, and the compound has a very good application value on the human lung adenocarcinoma cis-platinum-resistant strains. The compound can be further developed into a novel medicine for preventing and treating tumors.

Description

technical field [0001] The invention relates to the technical field of chemistry, in particular to a novel podophyllotoxin splicing antitumor active molecular compound and a preparation method and application thereof. Background technique [0002] Quinine, also known as cinchona alkaloid and cinchona frost, is the main alkaloid in the bark of Rubiaceae plant cinchona tree and its congeners. It not only has significant antimalarial effect, but also has significant antitumor activity. , can promote tumor cell apoptosis; Camptothecin (Camptothecin) is extracted and isolated from the dovetaceae plant Camptotheca, has significant anti-tumor activity, with camptothecin as the lead compound for structural modification to obtain a series of compounds, such as Irinotecan, topotecan, belonotecan, BNP-1350, and Gimatecan are now on the market for clinical use or in clinical trials; Indole is an important active skeleton that exists in many Among the natural active compounds, the most ...

AI Technical Summary

Problems solved by technology

At the same time, the most prominent biological activity of podophyllotoxin is anti-tumor activity, but its application is limited by strong adverse reactions due to its high toxicity. Therefore, a lot of structural modification work has been carried out on podophyllotoxin, and a series of podophyllotoxins with anti-tumor activity have been obtained. Toxin derivatives, such as etoposide (VP-16) and teniposide (VM-26), have become widely used anticancer drugs in clinical practice. Niposide has the disadvantages of narrow anti-tumor spectrum, poor water solubility, multi-drug resistance and severe gastrointestinal dysfunction, etc., and needs further structural modification or splicing with other active molecules to solve the above problems

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