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: Ieva Karpavičienė, Giedrė Valiulienė, Vytautas Raškevičius, Indrė Lebedytė, Algirdas Brukštus, Visvaldas Kairys, Rūta Navakauskienė, Inga Čikotienė
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 98 Pg. 30-48 (Jun 15 2015) ISSN: 1768-3254 [Electronic] France
• PMID: 26005022 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015. Published by Elsevier Masson SAS.

Chemical References

• Ketones

Topics

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