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

Magoulas, George E.; Rigopoulos, Andreas; Piperigkou, Zoi; Gialeli, Chrysostomi LU ; Karamanos, Nikos K.; Takis, Panteleimon G.; Troganis, Anastassios N.; Chrissanthopoulos, Athanassios; Maroulis, George and Papaioannou, Dionissios (2016) In Bioorganic Chemistry 66. p.132-144
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
A-549, Amides, Antiproliferative activity, l-DOPA, Lignans, MCF-7, MDA-MB-231, Phenol oxidative coupling
in
Bioorganic Chemistry
volume
66
pages
13 pages
publisher
Elsevier
external identifiers
  • scopus:84966706318
  • wos:000376505900017
ISSN
0045-2068
DOI
10.1016/j.bioorg.2016.04.003
language
English
LU publication?
yes
id
3f414da9-f28c-4550-aa23-9d4da03089de
date added to LUP
2016-09-27 13:20:22
date last changed
2017-07-30 05:15:21
@article{3f414da9-f28c-4550-aa23-9d4da03089de,
  abstract     = {<p>Two new diastereomeric lignan amides (4 and 5) serving as dimeric caffeic acid-l-DOPA hybrids were synthesized. The synthesis involved the FeCl<sub>3</sub>-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 (IC<sub>50</sub> 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 (IC<sub>50</sub> 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 (IC<sub>50</sub> 1-2 μM), probably as the result of slow hydrolysis of their methyl ester functions.</p>},
  author       = {Magoulas, George E. and Rigopoulos, Andreas and Piperigkou, Zoi and Gialeli, Chrysostomi and Karamanos, Nikos K. and Takis, Panteleimon G. and Troganis, Anastassios N. and Chrissanthopoulos, Athanassios and Maroulis, George and Papaioannou, Dionissios},
  issn         = {0045-2068},
  keyword      = {A-549,Amides,Antiproliferative activity,l-DOPA,Lignans,MCF-7,MDA-MB-231,Phenol oxidative coupling},
  language     = {eng},
  month        = {06},
  pages        = {132--144},
  publisher    = {Elsevier},
  series       = {Bioorganic Chemistry},
  title        = {Synthesis and antiproliferative activity of two diastereomeric lignan amides serving as dimeric caffeic acid-l-DOPA hybrids},
  url          = {http://dx.doi.org/10.1016/j.bioorg.2016.04.003},
  volume       = {66},
  year         = {2016},
}