Structural Modification Of Quinizarin And Camptothecin And Their Anti-tumor Activities

DNA topoisomerases are nuclear enzymes that can control and modify the topological states of DNA. Many types of interconversions between DNA topoisomers can be catalyzed by them. The functions of the enzymes have been implicated in various DNA transactions such as replication, transcription, recombination, and chromosome segregation at mitosis. There are two major topoisomerases, topo I and II, whose levels are higher in tumor cells than in normal cells. Unlike topoisomerase II, topoisomerase I is not a cell cycle-dependent enzyme, therefore, it is a more desirable cellular target for antitumor drug development.The paper described the procedures for the glycoconjugates synthesis of quinizarin and camptothecin. Quinizarin was coupled with a series of sugars (D-glycose, D-gaIacotose, D-lactose and D-xylose) through glycosylation. Camptothecin was coupled with 2-furonic acid, pyridinecarboxylic acid, niacin and isonicotinic acid through ester bond.The sugars are firstly transferred into the corresponding donors-2, 3, 4, 6-tetra-0-acetyl- -D-bromopyranose Before the glycosylation of quinizarin. Then the coupling reaction of the sugar donors with quinizarin at 1-0H and 4-0H was promoted by TEA6. Finally deprotection of the corresponding glycocongjugates afforded the target products. These ramifications were water soluble and ester soluble.Camptothec in was esterified with 2-furonic acid, pyridinecarboxylic acid, niacin and isonicotinic acid in the presence of DCC and 4-diImethylaminopyridine(DMAP) to provide the target compounds. Hydrolyze rate of these compounds at different pH were caculated by UV. These compounds show high hydrolytic ability in aqueous solutions at different pH.The compounds show good anti-tumor activity in vitro. Further determination of the bioactivities of all compounds are currently under researching.The structures of all the target products were characterized by IR, 1HNMR.