title: Syntheses, antiproliferative activity and theoretical characterization of acitretin-type retinoids with changes in the lipophilic part.
abstract: Acitretin analogs, incorporating changes in the lipophilic part, were efficiently synthesized from commercially available aromatic aldehydes or methyl ketones using the Wittig or Horner-Wadsworth-Emmons reaction. Their antiproliferative activity was evaluated against human breast MCF-7 epithelial cells. Analogs 3, 4, 8 and 11 exhibited strong, dose-dependent, antiproliferative activity on the tested cell line. Analog 3, incorporating three methoxy groups in the aromatic ring, exhibited the strongest inhibitory effect at 10 μM. High-level all electron conventional ab initio and density functional theory quantum chemical calculations were performed to obtain the molecular structure, electron charge distribution and polarization properties of all compounds of interest in this work. The most active analogs were planar and were characterized by larger dipole moments than the other synthesized molecules. Another factor of importance to the analysis of the activity of these molecules is the dipole polarizability.
authors.affiliation: Laboratory of Synthetic Organic Chemistry, Department of Chemistry, University of Patras, GR-265 04 Patras, Greece.
authors.forename: George E
authors.initials: GE
authors.lastname: Magoulas
authors.forename: Stavros E
authors.initials: SE
authors.lastname: Bariamis
authors.forename: Constantinos M
authors.initials: CM
authors.lastname: Athanassopoulos
authors.forename: Anastasios
authors.initials: A
authors.lastname: Haskopoulos
authors.forename: Petros G
authors.initials: PG
authors.lastname: Dedes
authors.forename: Marios G
authors.initials: MG
authors.lastname: Krokidis
authors.forename: Nikos K
authors.initials: NK
authors.lastname: Karamanos
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kletsas
authors.forename: Dionissios
authors.initials: D
authors.lastname: Papaioannou
authors.forename: George
authors.initials: G
authors.lastname: Maroulis
mesh_terms: D017255:Acitretin / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D011789:Quantum Theory; D012176:Retinoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D012176:Retinoids; D017255:Acitretin