Synthesis and Bioactivity of 1, 5- and 2, 6-Difunctionalized Amidoanthraquinones
| Autor: | Chen In-Been, 陳英斌 |
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| Rok vydání: | 2004 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 92 Telomerase is an attractive target for the design of new anticancer drugs. The activity is detected in 80~90% of tumor cells. Activation of telomerase in cancer cells enable the stabilization of telomere length and the ability for sustained cellular proliferation. Telomerase is thus an essential factor in cellular immortalization and consequent tumorigenesis. We have previously described the effects of a series of 1,5-bisthioanthraquinones, 1,5-bisacyloxyanthraquinones and 1,4-difunctionalized amidoanthraquinones on telomerase activity and interactive with hTERT (human telomerase reverse-transcriptases) promoter. The present study details the preparation of two distinct series of regioisomeric difunctionalized amidoanthraquinones substituted at the 1,5- and 2,6-positions, respectively. Their hTERT inhibition properties are reported and compared with Mitoxantrone and 1,5-bisacyloxyanthraquinones, that we need a further Bio-evaluation to discuss the SAR (structure activity relationship. Potent hTERT inhibition during SEAP (secreted alkaline phosphatase) assay is exhibited within MTT assay and we found MTT assay of most compounds were overexpress than SEAP assay). In addition, TRAP assay have been conducted to evaluate telomerase activity of G-quadruplex ligands as potent telomerase inhibitors. We found that the compound A9b indeed work out as a telomerase repressing agent compared to Mitoxantrone. Thus, our finding raises the possibility that these compounds might also have a role as potential anticancer agent. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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