Sulfur and selenium derivatives of quinazoline and pyrido[2,3-d]pyrimidine: Synthesis and study of their potential cytotoxic activity in vitro

被引：82

作者：

Moreno, Esther ^{[1
]}

Plano, Daniel ^{[1
]}

Lamberto, Iranzu ^{[1
]}

Font, Maria ^{[2
]}

Encio, Ignacio ^{[3
]}

Antonio Palop, Juan ^{[1
]}

Sanmartin, Carmen ^{[1
]}

机构：

[1] Univ Navarra, Dept Quim Organ & Farmaceut, Secc Sintesis, E-31008 Pamplona, Spain

[2] Univ Navarra, Dept Quim Organ & Farmaceut, Secc Modelizac Mol, E-31008 Pamplona, Spain

[3] Univ Publ Navarra, Dept Ciencias Salud, E-31008 Pamplona, Spain

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 47卷

关键词：

Cytotoxics; Antiproliferatives; Quinazolines; Pyridopyrimidines; TYROSINE KINASE INHIBITOR; BIOLOGICAL EVALUATION; DIHYDROFOLATE-REDUCTASE; ANTITUMOR-ACTIVITY; GROWTH-INHIBITION; APOPTOSIS; ANTICANCER; AGENTS; DISCOVERY; LEUKEMIA;

D O I：

10.1016/j.ejmech.2011.10.056

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis, cytotoxic activities and selectivities of 35 derivatives related to quinazoline and pyrido [2,3-d]pyrimidine are described. The synthesized compounds were screened in vitro against four tumoral cell lines leukemia (CCRF-CEM), colon (HT-29), lung (HTB-54) and breast (MCF-7) - and two cell lines derived from non-malignant cell lines, one mammary (18485) and one from bronchial epithelium (BEAS-2B). MCF-7 and HTB-54 were the most sensitive cell lines with GI(50) values below 10 mu M for eleven and ten compounds. respectively. Two compounds (2o and 3a) were identified that evoked a marked cytotoxic effect in all cell lines tested and one compound, 7h, was potent and selective against MCF-7. A preliminary study into the mechanism of the potent derivatives 2o, 3a and 7h indicated that the cytotoxic activities of these compounds might be mediated by inducing cell death without affecting cell cycle phases. (C) 2011 Elsevier Masson SAS. All rights reserved.

引用

页码：283 / 298

页数：16

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