TY - JOUR
TI - Synthesis and antiproliferative activity of two diastereomeric lignan amides serving as dimeric caffeic acid-l-DOPA hybrids
AU - Magoulas, G.E.
AU - Rigopoulos, A.
AU - Piperigkou, Z.
AU - Gialeli, C.
AU - Karamanos, N.K.
AU - Takis, P.G.
AU - Troganis, A.N.
AU - Chrissanthopoulos, A.
AU - Maroulis, G.
AU - Papaioannou, D.
JO - Bioorganic Chemistry
PY - 2016
VL - 66
TODO - null
SP - 132-144
PB - Academic Press Inc.
SN - 0045-2068, 1090-2120
TODO - 10.1016/j.bioorg.2016.04.003
TODO - caffeic acid;  catechol;  dimethyl 1 (3,4 dihydroxyphenyl) 6,7 dihydroxy 1,2 dihydronaphthalene 2,3 dicarboxylate;  DOPA;  lignan derivative;  methyl (1,2) 1 (3,4 dihydroxyphenyl) 2 ((3 (3,4 dihydroxyphenyl) 1 methoxy 1 oxopropan 2 yl)carbamoyl) 6,7 dihydroxy 1,2 dihydronaphthalene 3 carboxylate;  unclassified drug;  amide;  antineoplastic agent;  caffeic acid derivative;  levodopa;  lignan, antineoplastic activity;  antiproliferative activity;  Article;  breast cancer cell line;  cell proliferation;  column chromatography;  concentration response;  controlled study;  diastereoisomer;  drug synthesis;  enantiomer;  human;  human cell;  hydrolysis;  IC50;  lung cancer cell line;  oxidative coupling;  priority journal;  saponification;  stereochemistry;  structure activity relation;  chemical structure;  chemistry;  dose response;  drug effects;  drug screening;  MCF-7 cell line;  synthesis;  tumor cell culture, Amides;  Antineoplastic Agents;  Caffeic Acids;  Cell Proliferation;  Dose-Response Relationship, Drug;  Drug Screening Assays, Antitumor;  Humans;  Levodopa;  Lignans;  MCF-7 Cells;  Molecular Structure;  Structure-Activity Relationship;  Tumor Cells, Cultured
TODO - 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. © 2016 Elsevier Inc. All rights reserved.
ER -