The Synthesis Of Bone Target Antitumor Compounds Of Anthraquinone Components In Rhubarb

Rhubarb is the dry rhizome and root of Rheum Palmatum L., Rheum officinale Balg and Rheum officinalis Baill. As a traditional medicine, it possesses antitumor, antibacterial and anti-inflammatory activities. The main components in rhubarb are anthraquinones including emodin, chrysophanol and rhein. The condensed ring structure can insert into base pairs of DNA and interfere with the function of transcription and duplication. The mechanism of action is considered to be one of the main reasons of their cytotoxicity. Similar to the tetracycline, the anthraquinones have bone affinity property via hydroxyapative （HA） affinity experiment in vitro, so the anthraquinone components in rhubarb are ideal and novel bone target carriers.5-Fluorouracil is a broad-spectrum antitumor drug in clinic at present and tegafur is its prodrug with higher effect and lower toxicity. Both are antimetabolites which belong to pharmaceutical chemicals. The natural product podophyllotoxin and its derivatives have significant antitumor activities. They can inhibit microtubule and/or DNA topoisomeraseⅡ. The two kinds of antitumor drugs with different mechanism of action are linked to anthraquinone components in rhubarb in this paper, expecting to search new bone affinity antitumor compounds based on the synergistic effects of antitumor activities and bone affinity.Starting materials emodin, chrysophanol and rhein are linked to tegafur, as well as podophyllotoxin and its derivatives to prepare two series of antitumor compounds with bone affinity. In this paper, 20 intermediates and 12 target compounds are synthesized. Target compounds are all new and have not been reported up to now. All compounds were identified by ¹H-NMR and MS, and carried out the antitumor activity screening and bone affinity assay in vitro. The result shows that the bone affinity of 7 synthetic compounds is better than tetracycline, 5 intermediates and 1 target compounds are significant in the antitumor activity screening in vitro, and IC₅₀ can reach to 10^-7mol/L.