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

George E. Magoulas, Andreas Rigopoulos, Zoi Piperigkou, Chrysostomi Gialeli, Nikos K. Karamanos, Panteleimon G. Takis, Anastassios N. Troganis, Athanassios Chrissanthopoulos, George Maroulis, Dionissios Papaioannou

Research output: Contribution to journalArticlepeer-review

8 Citations (SciVal)

Abstract

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.

Original languageEnglish
Pages (from-to)132-144
Number of pages13
JournalBioorganic Chemistry
Volume66
DOIs
Publication statusPublished - 2016 Jun 1

Subject classification (UKÄ)

  • Biochemistry and Molecular Biology

Keywords

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

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