title: Synthesis and biological evaluation of a D-ring-contracted analogue of lamellarin D.
abstract: A D-ring contracted analogue of the strongly cytotoxic marine pyrrole alkaloid lamellarin D was synthesized and investigated for its antiproliferative action towards a wild type and a multidrug resistant (MDR) cancer cell line. The compound was found to inhibit tumor cell growth at submicromolar concentrations and showed a lower relative resistance in the MDR cell line than the antitumor drug camptothecin to which lamellarin D shows cross resistance and with which lamellarin D shares the same binding site.
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55128 Mainz, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Colligs
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55128 Mainz, Germany.
authors.forename: Steven Peter
authors.initials: SP
authors.lastname: Hansen
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55128 Mainz, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Imbri
authors.affiliation: Institute of Pharmacy and Biochemistry, Johannes Gutenberg-University, Staudinger Weg 5, 55128 Mainz, Germany.
authors.forename: Ean-Jeong
authors.initials: EJ
authors.lastname: Seo
authors.affiliation: Institute of Pharmacy and Biochemistry, Johannes Gutenberg-University, Staudinger Weg 5, 55128 Mainz, Germany.
authors.forename: Onat
authors.initials: O
authors.lastname: Kadioglu
authors.affiliation: Institute of Pharmacy and Biochemistry, Johannes Gutenberg-University, Staudinger Weg 5, 55128 Mainz, Germany. Electronic address: efferth@uni-mainz.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55128 Mainz, Germany. Electronic address: opatz@uni-mainz.de.
authors.forename: Till
authors.initials: T
authors.lastname: Opatz
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D062105:Molecular Docking Simulation; D016296:Mutagenesis; D017434:Protein Structure, Tertiary; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D006576:Heterocyclic Compounds, 4 or More Rings; D007546:Isoquinolines; D059004:Topoisomerase I Inhibitors; C455554:lamellarin D; D004264:DNA Topoisomerases, Type I
keywords: Alkaloid synthesis; Antitumor activity; Molecular docking; Natural product mimetics; Transition metal catalysis