Synthesis and in vitro antiproliferative evaluation of novel N-alkylated 6-isobutyl- and propyl pyrimidine derivatives.

Abstract

A series of novel N-alkylated C-6-isobutyl- or -propyl pyrimidine derivatives were synthesized and their antiproliferative effect was evaluated on a panel of tumor cell lines including leukemia cell line K562 and normal diploid human fibroblasts. N-methoxymethylated 5-methylpyrimidin-2,4-dione with di(benzyloxy)isobutyl at C-6 (14b) showed the strongest effect on the cell growth at micromolar concentrations. Mechanisms of action for the lipophilic compound 14b predicted in silico, pointed to its anticancer and antimetastatic potential exerted through inhibition of DNA or RNA polymerases and adhesion molecules. The latter mechanism has been supported in vitro for adherent tumor cell lines.

• Authors: Tatjana Gazivoda Kraljević, Nataša Ilić, Višnja Stepanić, Lana Sappe, Jasna Petranović, Sandra Kraljević Pavelić, Silvana Raić-Malić
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 24 Issue 13 Pg. 2913-7 (Jul 01 2014) ISSN: 1464-3405 [Electronic] England
• PMID: 24835982 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Pyrimidines

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Adhesion (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Fibroblasts (drug effects)
• HeLa Cells
• Hep G2 Cells
• Humans
• K562 Cells
• MCF-7 Cells
• Molecular Structure
• Pyrimidines (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship