Synthesis and antiproliferative activity of α-branched α,β-unsaturated ketones in human hematological and solid cancer cell lines

Ieva Karpavičienė; Giedrė Valiulienė; Vytautas Raškevičius; Indrė Lebedytė; Algirdas Brukštus; Visvaldas Kairys; Rūta Navakauskienė; Inga Čikotienė

doi:10.1016/j.ejmech.2015.05.012

Synthesis and antiproliferative activity of α-branched α,β-unsaturated ketones in human hematological and solid cancer cell lines

Eur J Med Chem. 2015 Jun 15:98:30-48. doi: 10.1016/j.ejmech.2015.05.012. Epub 2015 May 15.

Authors

Ieva Karpavičienė¹, Giedrė Valiulienė², Vytautas Raškevičius³, Indrė Lebedytė¹, Algirdas Brukštus¹, Visvaldas Kairys⁴, Rūta Navakauskienė⁵, Inga Čikotienė⁶

Affiliations

¹ Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, Vilnius, LT-03225, Lithuania.
² 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.
³ Department of Bioinformatics, Institute of Biotechnology, Vilnius University, V. Graičiūno 8, Vilnius, LT-02241, Lithuania.
⁴ 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.
⁵ Department of Molecular Cell Biology, Institute of Biochemistry, Vilnius University, Mokslininkų 12, Vilnius, LT-08662, Lithuania. Electronic address: ruta.navakauskiene@bchi.vu.lt.
⁶ Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, Vilnius, LT-03225, Lithuania. Electronic address: inga.cikotiene@chf.vu.lt.

PMID: 26005022
DOI: 10.1016/j.ejmech.2015.05.012

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.

Keywords: Antiproliferative activity; Apoptosis; Cell cycle arrest; Granulocytic differentiation; QSAR; α-branched α,β-unsaturated ketones.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Proliferation / drug effects*
Hematologic Neoplasms / pathology*
Humans
Ketones / chemical synthesis*
Ketones / chemistry
Ketones / pharmacology*
Neoplasms / pathology*
Quantitative Structure-Activity Relationship

Substances

Ketones