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

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.

NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng
A-549
Amides
Antiproliferative activity
l-DOPA
Lignans
MCF-7
MDA-MB-231
Phenol oxidative coupling

Rigopoulos, AndreasUniversity of Patras (författare)
Piperigkou, ZoiInstitute of Chemical Engineering Sciences (FORTH/ICE-HT) (författare)
Gialeli, ChrysostomiLund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups,University of Patras(Swepub:lu)med-cyg (författare)
Karamanos, Nikos K.University of Patras,Institute of Chemical Engineering Sciences (FORTH/ICE-HT) (författare)
Takis, Panteleimon G.University of Ioannina (författare)
Troganis, Anastassios N.University of Ioannina (författare)
Chrissanthopoulos, AthanassiosUniversity of Patras (författare)
Maroulis, GeorgeUniversity of Patras (författare)
Papaioannou, DionissiosUniversity of Patras (författare)
University of PatrasInstitute of Chemical Engineering Sciences (FORTH/ICE-HT) (creator_code:org_t)

Av författaren/redakt...: Magoulas, George ...; Rigopoulos, Andr ...; Piperigkou, Zoi; Gialeli, Chrysos ...; Karamanos, Nikos ...; Takis, Panteleim ...; visa fler...; Troganis, Anasta ...; Chrissanthopoulo ...; Maroulis, George; Papaioannou, Dio ...; visa färre...

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