title: Podoverine A--a novel microtubule destabilizing natural product from the Podophyllum species.
abstract: Natural products represent compound classes with high chemical and structural diversity and various biological activities. Libraries based on natural products are valuable starting point in the search for novel biologically active substances. Here we report on the identification of the natural product podoverine A from the plant Podophyllum versipelle Hance as a novel tubulin-acting agent. A natural product compound collection was subjected to a high-content screen that monitors changes in cytoskeleton and DNA and podoverine A was identified as inhibitor of mitosis. This natural product causes mitotic arrest and inhibits microtubule polymerization in vitro and in cells by targeting the vinca binding site on tubulin.
authors: Max-Planck-Institut für molekulare Physiologie, Abt. Chemische Biologie, Otto-Hahn-Str. 11, D-44227 Dortmund, Germany.
authors: Tuyen Thi Ngoc
authors: TT
authors: Tran
authors: Max-Planck-Institut für molekulare Physiologie, Abt. Chemische Biologie, Otto-Hahn-Str. 11, D-44227 Dortmund, Germany.
authors: Claas
authors: C
authors: Gerding-Reimers
authors: Max-Planck-Institut für molekulare Physiologie, Abt. Chemische Biologie, Otto-Hahn-Str. 11, D-44227 Dortmund, Germany.
authors: Beate
authors: B
authors: Schölermann
authors: Max-Planck-Institut für molekulare Physiologie, Abt. Chemische Biologie, Otto-Hahn-Str. 11, D-44227 Dortmund, Germany.
authors: Bettina
authors: B
authors: Stanitzki
authors: IMD Natural Solutions GmbH, Otto-Hahn-Str. 15, 44227 Dortmund, Germany.
authors: Thomas
authors: T
authors: Henkel
authors: Max-Planck-Institut für molekulare Physiologie, Abt. Chemische Biologie, Otto-Hahn-Str. 11, D-44227 Dortmund, Germany; Technische Universität Dortmund, Fakultät Chemie, Lehrbereich Chemische Biologie, Otto-Hahn-Str. 6, D-44227 Dortmund, Germany. Electronic address: herbert.waldmann@mpi-dortmund.mpg.de.
authors: Herbert
authors: H
authors: Waldmann
authors: Max-Planck-Institut für molekulare Physiologie, Abt. Chemische Biologie, Otto-Hahn-Str. 11, D-44227 Dortmund, Germany. Electronic address: slava.ziegler@mpi-dortmund.mpg.de.
authors: Slava
authors: S
authors: Ziegler
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D047309:Flavones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D011035:Podophyllum / Q000737:chemistry*; D058105:Polymerization / Q000187:drug effects; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001688:Biological Products; D047309:Flavones; D050257:Tubulin Modulators; C000596113:podoverine A
keywords: High content screening; Mitotic arrest; Natural products; Vinca binding site