title: Design, synthesis and structure-activity relationships of novel taxane-based multidrug resistance reversal agents.
abstract: A series of novel taxane-based multidrug resistance (MDR) reversal agents (TRAs) has been designed and synthesized. Structure-activity relationship (SAR) study clearly indicates that modification of the C-7 position with hydrophobic arenecarbonylcinnamoyl groups brings about high potency against drug efflux mediated by P-glycoprotein (P-gp). Six TRAs exhibit ability to modulate a wide range of ATP-binding cassette (ABC) transporters, such as P-gp, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP), which may serve as novel broad-spectrum modulators of ABC transporters.
authors.affiliation: Department of Chemistry, State University of New York at Stony Brook, Stony Brook, New York 11794-3400, USA. iojima@notes.cc.sunysb.edu
authors.forename: Iwao
authors.initials: I
authors.lastname: Ojima
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Borella
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Wu
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Bounaud
authors.forename: Cecilia Fumero
authors.initials: CF
authors.lastname: Oderda
authors.forename: Matthew
authors.initials: M
authors.lastname: Sturm
authors.forename: Michael L
authors.initials: ML
authors.lastname: Miller
authors.forename: Subrata
authors.initials: S
authors.lastname: Chakravarty
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.forename: Qing
authors.initials: Q
authors.lastname: Huang
authors.forename: Paula
authors.initials: P
authors.lastname: Pera
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Brooks
authors.forename: Maria R
authors.initials: MR
authors.lastname: Baer
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Bernacki
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D020650:Combinatorial Chemistry Techniques; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008942:Mitoxantrone / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D008942:Mitoxantrone; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D017239:Paclitaxel; D043823:Taxoids; C421109:multidrug resistance-associated protein 1