title: SAR studies on hydropentalene derivatives--Important core units of biologically active tetramic acid macrolactams and ptychanolides.
abstract: Structurally diverse bicyclo[3.3.0]octanes were prepared and tested for their biological activity. Both the antiproliferative activity and the results of phenotypic characterization varied with the substitution patterns. Two derivatives displayed high inhibitory (IC50 ≤3μM) activity against the L-929 cell line, but differed in their mode of action. A cluster analysis with impedance profiling data showed the two compounds in relationship to microtubule interfering compounds. In PtK2 cells treated with both derivatives a perturbing effect on the microtubular network was observed, whereas the actin cytoskeleton in incubated PtK2 cells was disturbed only by one compound. The effects on tubulin and actin polymerization could be confirmed by in vitro polymerization experiments.
authors.affiliation: Institut für Organische Chemie der Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Lutz
authors.affiliation: Institut für Organische Chemie der Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Mannchen
authors.affiliation: Institut für Organische Chemie der Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Krebs
authors.affiliation: Institut für Organische Chemie der Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany.
authors.forename: Natja
authors.initials: N
authors.lastname: Park
authors.affiliation: Institut für Organische Chemie der Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Krüger
authors.affiliation: Department of Chemical Biology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
authors.forename: Aruna
authors.initials: A
authors.lastname: Raja
authors.affiliation: Department of Chemical Biology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany. Electronic address: florenz.sasse@helmholtz-hzi.de.
authors.forename: Florenz
authors.initials: F
authors.lastname: Sasse
authors.affiliation: Institut für Organische Chemie der Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Baro
authors.affiliation: Institut für Organische Chemie der Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany. Electronic address: sabine.laschat@oc.uni-stuttgart.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Laschat
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D047029:Lactams, Macrocyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008968:Molecular Conformation; D011760:Pyrrolidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001643:Bridged Bicyclo Compounds; D047029:Lactams, Macrocyclic; D011760:Pyrrolidinones; C009435:tetramic acid
keywords: Biological activity; Click chemistry; Hydropentalene; Structure–activity relationships; Synthesis