Design and Synthesis of Amido- and Carbamoyl- anthraquinones as Potential Antitumor Agents
| Autor: | Wan-Ru Chen, 陳婉茹 |
|---|---|
| Rok vydání: | 2005 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 93 Most antitumor agents are highly cytotoxic but not selective. Increasing the lignad selectivity to specific DNA sequences may reduce their toxicity and other adverse effects. Drugs containing 9,10-anthracenedione, such as ametantrone and mitoxantrone, have been used as anti-tumor agents for a long time. Now mitoxantrone, which contains a planar anthraquinone skeleton, is a clinically useful antitumor agent. The planar characteristics of the core structure 9,10-anthracenedione are necessary for molecular recognition and binding into the base pairs of DNA helix to affect transcription and replication processes of the cell. This intercalative interaction may serve as an anchor for intercalating drugs at specific sites of DNA base pair followed by cell-killing. With the aims to increase the DNA affinity and selectivity, a series of l,4-bis[(2-aminoethyl)amino] substituted9,l0-anthracenedione was designed and prepared by parallel synthesis. We reserve the planar characteristics of the core structure 9,10-anthracenedione,and the 2-(aminoethyl)amino of mitoxantrone. The 2-(aminoethyl)amino could be linked a variety of amino acids. The side chain amino acids will create ionic interaction with the ribose phosphates of the nucleic acids. Howevre, the peptide backbone is not stable to proteolytic degradation. Recently an increasing amount of attention has focused on the application of the carbamate moiety as a replacement for the amide bond in peptidomimetics. We reduced the amino acid to amino alcohol and introduced a carbonyloxy group. In order to introduce the carbonyloxy monomer to anthracqueinone skeleton, we are trying to develop a convenient general method for parallel synthesis. Several novel anthracqueinone derivatives showed significant cytotoxicoty against different houmor cancer cell lines. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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