title: Combination of Synthetic Chemistry and Live-Cell Imaging Identified a Rapid Cell Division Inhibitor in Tobacco and Arabidopsis thaliana.
abstract: Cell proliferation is crucial to the growth of multicellular organisms, and thus the proper control of cell division is important to prevent developmental arrest or overgrowth. Nevertheless, tools for controlling cell proliferation are still poor in plant. To develop novel tools, we focused on a specific compound family, triarylmethanes, whose members show various antiproliferative activities in animals. By combining organic chemistry to create novel and diverse compounds containing the triarylmethyl moiety and biological screens based on live-cell imaging of a fluorescently labeled tobacco Bright Yellow-2 (BY-2) culture cell line (Nicotiana tabacum), we isolated (3-furyl)diphenylmethane as a strong but partially reversible inhibitor of plant cell division. We also found that this agent had efficient antiproliferative activity in developing organs of Arabidopsis thaliana without causing secondary defects in cell morphology, and induced rapid cell division arrest independent of the cell cycle stage. Given that (3-furyl)diphenylmethane did not affect the growth of a human cell line (HeLa) and a budding yeast (Saccharomyces cerevisiae), it should act specifically on plants. Taking our results together, we propose that the combination of desired chemical synthesis and detailed biological analysis is an effective tool to create novel drugs, and that (3-furyl)diphenylmethane is a specific antiproliferative agent for plants.
authors: Institute of Transformative Bio-Molecules (ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8601 Japan m-ueda@itbm.nagoya-u.ac.jp mnambo@itbm.nagoya-u.ac.jp.|These authors contributed equally to this work.
authors: Masakazu
authors: M
authors: Nambo
authors: Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8602 Japan.|JST, ERATO Higashiyama Live-Holonics Project, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8602 Japan.
authors: Daisuke
authors: D
authors: Kurihara
authors: Institute of Transformative Bio-Molecules (ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8601 Japan.
authors: Tomomi
authors: T
authors: Yamada
authors: Institute of Transformative Bio-Molecules (ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8601 Japan.|Laboratory of Animal Physiology, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8601 Japan.
authors: Taeko
authors: T
authors: Nishiwaki-Ohkawa
authors: Laboratory of Animal Physiology, Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8601 Japan.
authors: Naoya
authors: N
authors: Kadofusa
authors: Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8602 Japan.
authors: Yusuke
authors: Y
authors: Kimata
authors: Institute of Transformative Bio-Molecules (ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8601 Japan.
authors: Keiko
authors: K
authors: Kuwata
authors: Laboratory of Plant Growth Regulation, Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), Takayama-cho 8916-5, Ikoma, Nara, 630-0192 Japan.|JST, CREST, Takayama-cho 8916-5, Ikoma, Nara, 630-0192 Japan.
authors: Masaaki
authors: M
authors: Umeda
authors: Institute of Transformative Bio-Molecules (ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8601 Japan m-ueda@itbm.nagoya-u.ac.jp mnambo@itbm.nagoya-u.ac.jp.|Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8602 Japan.|These authors contributed equally to this work.
authors: Minako
authors: M
authors: Ueda
mesh_terms: D017360:Arabidopsis / Q000166:cytology*; D001559:Benzhydryl Compounds / Q000737:chemistry; D002453:Cell Cycle; D002455:Cell Division; D049109:Cell Proliferation; D002470:Cell Survival; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D006367:HeLa Cells; D057166:High-Throughput Screening Assays; D006801:Humans; D057054:Molecular Imaging / Q000379:methods*; D009928:Organ Specificity; D014026:Nicotiana / Q000166:cytology*
chemical_list: D001559:Benzhydryl Compounds; C010129:diphenylmethane
keywords: 
  Arabidopsis thaliana
  ; Cell division inhibitor; Live-cell imaging; Organic chemistry; Tobacco BY-2 cell; Triarylmethane