Synthesis and biological evaluation of a D-ring-contracted analogue of lamellarin D

  • Bioorg Med Chem. 2017 Nov 15;25(22):6137-6148. doi: 10.1016/j.bmc.2017.02.005.
Vanessa Colligs  1 ,  Steven Peter Hansen  1 ,  Dennis Imbri  1 ,  Ean-Jeong Seo  2 ,  Onat Kadioglu  2 ,  Thomas Efferth  3 ,  Till Opatz  4
Affiliations
  • 1. Institute of Organic Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55128 Mainz, Germany.
  • 2. Institute of Pharmacy and Biochemistry, Johannes Gutenberg-University, Staudinger Weg 5, 55128 Mainz, Germany.
  • 3. Institute of Pharmacy and Biochemistry, Johannes Gutenberg-University, Staudinger Weg 5, 55128 Mainz, Germany. Electronic address: [email protected].
  • 4. Institute of Organic Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55128 Mainz, Germany. Electronic address: [email protected].
PMID: 28233677 DOI: 10.1016/j.bmc.2017.02.005
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.

Keywords
Alkaloid synthesis; Antitumor activity; Molecular docking; Natural product mimetics; Transition metal catalysis.