Τίτλος:
Synthesis and antiproliferative activity of two diastereomeric lignan amides serving as dimeric caffeic acid-l-DOPA hybrids
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Magoulas, G.E.
Rigopoulos, A.
Piperigkou, Z.
Gialeli, C.
Karamanos, N.K.
Takis, P.G.
Troganis, A.N.
Chrissanthopoulos, A.
Maroulis, G.
Papaioannou, D.
Περιοδικό:
Bioorganic Chemistry
Εκδότης:
Academic Press Inc.
Λέξεις-κλειδιά:
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
DOI:
10.1016/j.bioorg.2016.04.003
