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A novel class of highly potent multidrug resistance reversal agents: disubstituted adamantyl derivatives
Kyung Hoon Min1, Yan Xia, Eun Kyung Kim
1College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea. khmin@cau.ac.kr
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.
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