title: New artesunic acid homodimers: potent reversal agents of multidrug resistance in leukemia cells.
abstract: To evade the problem of multidrug resistance, hybridization of natural products in dimers is considered as an effective method. After the successful synthesis of three artesunic acid homodimers connected by different types of chemical linkers, we analyzed their activity against human CCRF-CEM and multidrug-resistant P-glycoprotein-overexpressing CEM/ADR 5000 leukemia cells and observed, that multidrug resistant cells were not cross-resistant to the new compounds. Collateral sensitivity was observed for artesunic acid homodimer 2. The obtained results deliver valuable information about the linker's structure which is required for homodimers to be highly cytotoxic.
authors.affiliation: Institute of Organic Chemistry I, University of Erlangen-Nuremberg, Henkestrasse 42, 91054 Erlangen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Reiter
authors.forename: Astrid
authors.initials: A
authors.lastname: Herrmann
authors.forename: Aysun
authors.initials: A
authors.lastname: Çapci
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
authors.forename: Svetlana B
authors.initials: SB
authors.lastname: Tsogoeva
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D037621:Artemisinins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013386:Succinates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; D013386:Succinates; C111789:artesunic acid