title: Synthesis and antiproliferative activity of α-branched α,β-unsaturated ketones in human hematological and solid cancer cell lines.
abstract: A series of α-branched α,β-unsaturated ketones were prepared via boron trifluoride etherate mediated reaction between arylalkynes and carboxaldehydes. The evaluation of the antiproliferative activity over hematological (NB4) and solid cancer (A549, MCF-7) cell lines provided a structure-activity relationship. 5-Parameter QSAR equations were built which were able to explain 80%-92% of the variance in activity. The resulting selective lead compound showed IC50 value 0.6 μM against the hematological cell line and did not cause apoptosis, but blocked cell cycle in G0/G1. Moreover, it was demonstrated that this compound enhances and accelerates retinoic acid induced granulocytic differentiation.
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, Vilnius, LT-03225, Lithuania.
authors.forename: Ieva
authors.initials: I
authors.lastname: Karpavičienė
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, Vilnius, LT-03225, Lithuania; Department of Molecular Cell Biology, Institute of Biochemistry, Vilnius University, Mokslininkų 12, Vilnius, LT-08662, Lithuania.
authors.forename: Giedrė
authors.initials: G
authors.lastname: Valiulienė
authors.affiliation: Department of Bioinformatics, Institute of Biotechnology, Vilnius University, V. Graičiūno 8, Vilnius, LT-02241, Lithuania.
authors.forename: Vytautas
authors.initials: V
authors.lastname: Raškevičius
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, Vilnius, LT-03225, Lithuania.
authors.forename: Indrė
authors.initials: I
authors.lastname: Lebedytė
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, Vilnius, LT-03225, Lithuania.
authors.forename: Algirdas
authors.initials: A
authors.lastname: Brukštus
authors.affiliation: Department of Bioinformatics, Institute of Biotechnology, Vilnius University, V. Graičiūno 8, Vilnius, LT-02241, Lithuania; Department of Applied Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, Vilnius, LT-03225, Lithuania.
authors.forename: Visvaldas
authors.initials: V
authors.lastname: Kairys
authors.affiliation: Department of Molecular Cell Biology, Institute of Biochemistry, Vilnius University, Mokslininkų 12, Vilnius, LT-08662, Lithuania. Electronic address: ruta.navakauskiene@bchi.vu.lt.
authors.forename: Rūta
authors.initials: R
authors.lastname: Navakauskienė
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, Vilnius, LT-03225, Lithuania. Electronic address: inga.cikotiene@chf.vu.lt.
authors.forename: Inga
authors.initials: I
authors.lastname: Čikotienė
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019337:Hematologic Neoplasms / Q000473:pathology*; D006801:Humans; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009369:Neoplasms / Q000473:pathology*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D007659:Ketones
keywords: Antiproliferative activity; Apoptosis; Cell cycle arrest; Granulocytic differentiation; QSAR; α-branched α,β-unsaturated ketones