Synthesis of imidazole analogs as ABCB1/ABCG2 inhibitors and the study of their structure-activity relationship
| Autor: | LI,HAI-CHEN, 李海辰 |
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| Rok vydání: | 2016 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 104 During the treatment of cancer, multidrug resistance (MDR) is one of the most intractable problems. Multidrug resistance is often caused by the overexpression of ABC transporter (ATP-binding cassette transporter) ABCB1, ABCC1, ABCG2 which result in cancer drug to be exported out of the cell, rendering chemotherapy ineffective. As an effort to counteract this problem, we first took the substructure of tariquidar,2-benzamido-N-phenylbenzamide as the lead compound, and synthesize derivatives with different functional groups. While the synthesis of these derivatives were not as successful, we then synthesized compounds derived from three imidazole inhibitors screened at Professor Chung-Pu Wu’s laboratory, Chang Gung University. The ABC transporter protein inhibitory activity, showed that the nitrile substituting derivative demonstrated the best activity and when carboxyl group was esterified, the activity increased as well. The inhibitory activity of compounds showed that the hydrophobic group was preferred for ABCG2 inhibition. Neither electronic nor structure size of substituents appeared to affect the ABC transporter inhibition. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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