The New Antitumor Drugs Of Curcumin Derivatives And Gambogic Acid Derivatives:Syntheses And The Studies Of Antitumor Activity

There were mainly cell poisonous drugs of the antitumor drugs on the market all the time. During in the treatment the patients were very painful because of cell poisonous drugs have the identification poorly for cancer cells, strong response of Side-effect and appearing drug resistance easily. Even if the cancer was treated successfully, the patients would be in face of cancer recurrence at any time. So people have to look to the targeted drugs. Traditional Chinese medicine is one of the sources of targeted drugs. Our experiment topic selection is Chinese traditional medicine of curcumin and gambogic acid. Gambogic acid is a compound which has a high antitumor activity and good cell selection. The experimental results showed that gambogic acid had strong antitumor activity to a wide variety of tumor and has a low side-effect In the effective dose range. Gambogic acid is a very high selectivity drug to inhibit tumor cells but has no effect to normal animal hematopoietic system and immune function. It provides a new prospect and might inspire a new anti-cancer mechanism for looking for new antitumor drugs. So is curcumin.We designed and synthesized curcumin and gambogic caid derivatives by curcumin and gamgobic acid as raw materials. The compounds were isolated by repeated column chromatography (CC) on sillca gel, RP-18, as well as by preparative thin layer chromatography (PTLC) and recrystallization. The structures of these compounds were elucidated by means of spectroscopic methods including1H-NMR, MS/ESI and single-crystal X-ray diffraction techniques.The water-soluble of curcumin is poor, so we synthetized8compounds, including7new compounds, for improving the water-soluble of curcumin derivatives. And later we tested the antitumor activity of6curcumin derivatives. In addition to the antitumor activity of curcumin pyrazole was better than curcumin, the rest of the compounds’were sharp decline. For the water-soluble of gambogic acid is also poor, we improved the water-soluble by synthesizing gambogic acid derivatives. We mainly bedecked the carboxyl of gambogic acid molecules, synthesizing4amide compounds of gambogic acid and1ester compound of gambogic acid. We deoxidaed the compound of W8with NaBH4, obtaining W9. It was for reseaching the antitumor activity of the compound which was deoxidaed.The antitumor activity was evaluated in vitro by MTT assay. In antitumor activity test for the compounds, we used the MTT method and selected five tumor cell lines, the A549(human lung cancer), HCT116(human colon cancer), ZR-75-30(human breast cancer), PANT-1(human pancreas cancer) and HepG2(human hepatoma cells). Cytotoxicity experiments in vitro confirmed structure-activity relationship of curcumin and gambogic acid. We found compounds of W8, W11and W12showed excellent cytotoxic activity in new synthetic derivatives. They have reached the level of pharmaceutical activity.