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

Tatjana Gazivoda Kraljević; Nataša Ilić; Višnja Stepanić; Lana Sappe; Jasna Petranović; Sandra Kraljević Pavelić; Silvana Raić-Malić

doi:10.1016/j.bmcl.2014.04.079

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

Tatjana Gazivoda Kraljević, Nataša Ilić, Višnja Stepanić, Lana Sappe, Jasna Petranović, Sandra Kraljević Pavelić, Silvana Raić-Malić

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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.

Original language	English
Pages (from-to)	2913-2917
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	13
DOIs	https://doi.org/10.1016/j.bmcl.2014.04.079
State	Published - 1 Jul 2014
Externally published	Yes

Bibliographical note

Funding Information:
Support of this study by the Ministry of Science, Education and Sports of the Republic of Croatia (Projects #125-0982464-2925, #335-0000000-3532 and #098-0982464-2511) is gratefully acknowledged.

Funding

Support of this study by the Ministry of Science, Education and Sports of the Republic of Croatia (Projects #125-0982464-2925, #335-0000000-3532 and #098-0982464-2511) is gratefully acknowledged.

Funders	Funder number
Ministarstvo Obrazovanja, Znanosti i Sporta	335-0000000-3532, 098-0982464-2511, 125-0982464-2925

Keywords

Antiproliferative evaluation
C-6-isobutyl pyrimidine
C-6-propyl pyrimidine
In silico analysis
N-Alkylated pyrimidine derivatives

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10.1016/j.bmcl.2014.04.079

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title = "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.",

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note = "Funding Information: Support of this study by the Ministry of Science, Education and Sports of the Republic of Croatia (Projects #125-0982464-2925, #335-0000000-3532 and #098-0982464-2511) is gratefully acknowledged. ",

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doi = "10.1016/j.bmcl.2014.04.079",

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AU - Gazivoda Kraljević, Tatjana

AU - Ilić, Nataša

AU - Stepanić, Višnja

AU - Sappe, Lana

AU - Petranović, Jasna

AU - Kraljević Pavelić, Sandra

AU - Raić-Malić, Silvana

N1 - Funding Information: Support of this study by the Ministry of Science, Education and Sports of the Republic of Croatia (Projects #125-0982464-2925, #335-0000000-3532 and #098-0982464-2511) is gratefully acknowledged.

PY - 2014/7/1

Y1 - 2014/7/1

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

Funding

Keywords

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