A novel class of highly potent multidrug resistance reversal agents: disubstituted adamantyl derivatives

  • Bioorg Med Chem Lett. 2009 Sep 15;19(18):5376-9. doi: 10.1016/j.bmcl.2009.07.127.
Kyung Hoon Min  1 ,  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
Affiliations
  • 1. College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea. [email protected]
PMID: 19679475 DOI: 10.1016/j.bmcl.2009.07.127
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.