title: A novel class of highly potent multidrug resistance reversal agents: disubstituted adamantyl derivatives.
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.
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea. khmin@cau.ac.kr
authors.forename: Kyung Hoon
authors.initials: KH
authors.lastname: Min
authors.forename: Yan
authors.initials: Y
authors.lastname: Xia
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Kim
authors.forename: Yinglan
authors.initials: Y
authors.lastname: Jin
authors.forename: Navneet
authors.initials: N
authors.lastname: Kaur
authors.forename: Eun Seon
authors.initials: ES
authors.lastname: Kim
authors.forename: Dae Kyong
authors.initials: DK
authors.lastname: Kim
authors.forename: Hwa Young
authors.initials: HY
authors.lastname: Jung
authors.forename: Yongseok
authors.initials: Y
authors.lastname: Choi
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Park
authors.forename: Yong Ki
authors.initials: YK
authors.lastname: Min
authors.forename: Kiho
authors.initials: K
authors.lastname: Lee
authors.forename: Kyeong
authors.initials: K
authors.lastname: Lee
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000218:Adamantane / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D012509:Sarcoma / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D000218:Adamantane