2. Academic Validation
  3. Design, synthesis and anti-malarial activities of synthetic analogs of biselyngbyolide B, a Ca2+ pump inhibitor from marine cyanobacteria

Design, synthesis and anti-malarial activities of synthetic analogs of biselyngbyolide B, a Ca2+ pump inhibitor from marine cyanobacteria

  • Bioorg Med Chem Lett. 2018 Feb 1;28(3):298-301. doi: 10.1016/j.bmcl.2017.12.050.
Eisuke Sato 1,  Maho Morita 2,  Haruo Ogawa 3,  Masato Iwatsuki 4,  Rei Hokari 4,  Aki Ishiyama 4,  Satoshi Ōmura 4,  Arihiro Iwasaki 1,  Kiyotake Suenaga 5
Affiliations

Affiliations

  • 1 Department of Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi 3-14-1, Kohoku-ku, Yokohama 223-8522, Japan.
  • 2 Department of Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi 3-14-1, Kohoku-ku, Yokohama 223-8522, Japan; Institute of Molecular and Cellular Bioscience, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
  • 3 Institute of Molecular and Cellular Bioscience, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
  • 4 Research Center for Tropical Diseases, Kitasato Institute for Life Science, and Graduate School of Infection Control Science, Kitasato University, 5-9-1, Shirokane Minato-ku, Tokyo 108-8641, Japan.
  • 5 Department of Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi 3-14-1, Kohoku-ku, Yokohama 223-8522, Japan. Electronic address: suenaga@chem.keio.ac.jp.
PMID: 29292225 DOI: 10.1016/j.bmcl.2017.12.050
Abstract

Biselyngbyaside, an 18-membered Macrolide glycoside from marine cyanobacteria, and its derivatives are known to be sarco/endoplasmic reticulum CA2+ ATPase (SERCA) inhibitors. Recently, a SERCA orthologue of the malaria Parasite, PfATP6, has attracted attention as a malarial drug target. To provide a novel drug lead, we designed new synthetic analogs of biselyngbyolide B, the aglycone of biselyngbyaside, based on the co-crystal structure of SERCA with biselyngbyolide B, and synthesized them using the established synthetic route for biselyngbyolide B. Their biological activities against malarial parasites were evaluated.

Keywords

Biselyngbyaside; Biselyngbyolide; PfATP6; SERCA; Structure–activity relationships.

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