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A novel class of highly potent multidrug resistance reversal agents: Disubstituted adamantyl derivatives |
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| Authors: | Kyung Hoon Min Yan Xia Eun Kyung Kim Yinglan Jin Navneet Kaur Eun Seon Kim Dae Kyong Kim Hwa Young Jung Yongseok Choi Mi-Kyung Park Yong Ki Min Kiho Lee Kyeong Lee |
| Affiliation: | aCollege of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea;bKorea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea;cKorea University of Science and Technology, Daejeon, 305-333, Republic of Korea;dSchool of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of Korea;eKorea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea |
| Abstract: | Novel disubstituted adamantyl derivatives were synthesized and evaluated in a P-glycoprotein dependent multidrug resistance cancer cell line. The hit to lead optimization provided potent MDR reversal agents. Some potent adamantyl derivatives were more than 10-fold more potent than verapamil without considerable intrinsic cytotoxicity. The 3-trifluorophenyl derivative 14f did not affect the metabolism of CYP450 3A4, whereas most of MDR revertants had a weak inhibitory effect. |
| Keywords: | Multidrug resistance MES-SA/DX5 ABC transporter P-glycoprotein Adamantane CYP3A4 |
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