Synthesis and biological evaluation of cyanoaziridine phosphine oxides and phosphonates with antiproliferative activity

被引：22

作者：

Carraminana, Victor ^{[1
,2
]}

Ochoa de Retana, Ana M. ^{[1
,2
]}

Velez del Burgo, Ander ^{[1
,2
]}

de los Santos, Jesus M. ^{[1
,2
]}

Palacios, Francisco ^{[1
,2
]}

机构：

[1] Univ Basque Country UPV EHU, Dept Quim Organ 1, Fac Farm, Paseo Univ 7, Vitoria 01006, Spain

[2] Univ Basque Country UPV EHU, Ctr Invest & Estudios Avanzados Lucio Lascaray, Paseo Univ 7, Vitoria 01006, Spain

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2019年 / 163卷

关键词：

2H-azirine; Phosphorus substituted cyanoaziridines; Antiproliferative effect; ASYMMETRIC-SYNTHESIS; BETA-AMINOPHOSPHONATES; AZIRIDINES; INHIBITORS; 2H-AZIRINES; ACID; FERMENTATION; ANTIBIOTICS; ANTICANCER; GENERATION;

D O I：

10.1016/j.ejmech.2018.12.002

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

This work reports an efficient diastereoselective synthetic methodology for the preparation of phosphorus substituted cyanoaziridines through the nucleophilic addition of TMSCN, as cyanide source, to the C-N double bond of 2H-azirine derivatives. The aziridine ring, in these novel cyanoaziridines, can be activated by simple N-tosylation or N-acylation. In addition, the cytotoxic effect on cell lines derived from human lung adenocarcinoma (A549) and human embryonic kidney (HEK293) was also screened. N-H and N-Substituted cyanoaziridines showed excellent activity against the A549 cell line in vitro. Moreover, selectivity towards cancer cell (A549) over (HEK293), and non-malignant cells (MCR-5) has been observed. (C) 2018 Elsevier Masson SAS. All rights reserved.

引用

页码：736 / 746

页数：11

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