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Synthesis and antiproliferative activity of two diastereomeric lignan amides serving as dimeric caffeic acid-l-DOPA hybrids

Author:
  • George E. Magoulas
  • Andreas Rigopoulos
  • Zoi Piperigkou
  • Chrysostomi Gialeli
  • Nikos K. Karamanos
  • Panteleimon G. Takis
  • Anastassios N. Troganis
  • Athanassios Chrissanthopoulos
  • George Maroulis
  • Dionissios Papaioannou
Publishing year: 2016-06-01
Language: English
Pages: 132-144
Publication/Series: Bioorganic Chemistry
Volume: 66
Document type: Journal article
Publisher: Elsevier

Abstract english

Two new diastereomeric lignan amides (4 and 5) serving as dimeric caffeic acid-l-DOPA hybrids were synthesized. The synthesis involved the FeCl3-mediated phenol oxidative coupling of methyl caffeate to afford trans-diester 1a as a mixture of enantiomers, protection of the catechol units, regioselective saponification, coupling with a suitably protected l-DOPA derivative, separation of the two diastereomers thus obtained by flash column chromatography and finally global chemoselective deprotection of the catechol units. The effect of hybrids 4 and 5 and related compounds on the proliferation of two breast cancer cell lines with different metastatic potential and estrogen receptor status (MDA-MB-231 and MCF-7) and of one epithelial lung cancer cell line, namely A-549, was evaluated for concentrations ranging from 1 to 256 μM and periods of treatment of 24, 48 and 72 h. Both hybrids showed interesting and almost equipotent antiproliferative activities (IC50 64-70 μM) for the MDA-MB-231 cell line after 24-48 h of treatment, but they were more selective and much more potent (IC50 4-16 μM) for the MCF-7 cells after 48 h of treatment. The highest activity for both hybrids and both breast cancer lines was observed after 72 h of treatment (IC50 1-2 μM), probably as the result of slow hydrolysis of their methyl ester functions.

Keywords

  • Biochemistry and Molecular Biology
  • A-549
  • Amides
  • Antiproliferative activity
  • l-DOPA
  • Lignans
  • MCF-7
  • MDA-MB-231
  • Phenol oxidative coupling

Other

Published
  • Protein Chemistry, Malmö
  • ISSN: 0045-2068
E-mail: chrysostomi [dot] gialeli [at] med [dot] lu [dot] se

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