title: Inhibition of ABCG2-mediated drug efflux by naphthopyrones from marine crinoids.
abstract: Five new naphthopyrones (1-5) along with the known compounds TMC-256A1, 5,8-dihydroxy-6-methoxy-2-propyl-4H-naphtho[2,3-b]pyran-4-one, TMC-256C1, comaparvin, 6-methoxycomaparvin, and 6-methoxycomaparvin 5-methyl ether (6-11) were isolated from crinoids of the family Comasteridae. All compounds were tested for their ability to inhibit the multidrug transporter ABCG2, which plays a role in drug resistance. Six of the seven angular naphthopyrones showed moderate activity with <60% inhibition of ABCG2-mediated transport as compared to the positive control fumitremorgin C. None of the linear naphthopyrones inhibited ABCG2-mediated efflux.
authors.affiliation: Molecular Targets Laboratory, NCI-Frederick, Frederick, MD 21702, USA.
authors.forename: Heidi R
authors.initials: HR
authors.lastname: Bokesch
authors.forename: Laura K
authors.initials: LK
authors.lastname: Cartner
authors.forename: Richard W
authors.initials: RW
authors.lastname: Fuller
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Wilson
authors.forename: Curtis J
authors.initials: CJ
authors.lastname: Henrich
authors.forename: James A
authors.initials: JA
authors.lastname: Kelley
authors.forename: Kirk R
authors.initials: KR
authors.lastname: Gustafson
authors.forename: James B
authors.initials: JB
authors.lastname: McMahon
authors.forename: Tawnya C
authors.initials: TC
authors.lastname: McKee
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004447:Echinodermata / Q000737:chemistry*; D006801:Humans; D008968:Molecular Conformation; D009281:Naphthalenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009281:Naphthalenes; D009363:Neoplasm Proteins; D011753:Pyrones