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

Eur J Med Chem. 2019 Feb 1:163:736-746. doi: 10.1016/j.ejmech.2018.12.002.

Victor Carramiñana ¹, Ana M Ochoa de Retana ¹, Ander Vélez Del Burgo ¹, Jesús M de Los Santos ², Francisco Palacios ³

Affiliations

1 Departamento de Química Orgánica I, Facultad de Farmacia and Centro de Investigaciones y Estudios Avanzados "Lucio Lascaray", University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006, Vitoria, Spain.
2 Departamento de Química Orgánica I, Facultad de Farmacia and Centro de Investigaciones y Estudios Avanzados "Lucio Lascaray", University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006, Vitoria, Spain. Electronic address: jesus.delossantos@ehu.eus.
3 Departamento de Química Orgánica I, Facultad de Farmacia and Centro de Investigaciones y Estudios Avanzados "Lucio Lascaray", University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006, Vitoria, Spain. Electronic address: francisco.palacios@ehu.eus.

PMID: 30576904 DOI: 10.1016/j.ejmech.2018.12.002

Abstract

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.

Keywords

2H-azirine; Antiproliferative effect; Phosphorus substituted cyanoaziridines.

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