beta-amino alcohols and their respective 2-phenyl-N-alkyl aziridines as potential DNA minor groove binders

Autor(es):Mostrar menos -

Vaidergorn, Miguel M. ^[1] ; Carneiro, Zumira A. ^[2] ; Lopes, Carla D. ^[2] ; de Albuquerque, Sergio ^[2] ; Reis, Felipe C. C. ^[3] ; Nikolaou, Sofia ^[3] ; e Mello, Juliana F. R. ^[4] ; Genesi, Giovani L. ^[4] ; Trossini, Gustavo H. G. ^[4] ; Ganesan, A. ^[5] ; Emery, Flavio S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Pharmaceut Sci, Sch Pharmaceut Sci Ribeirao Preto FCFRP, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Dept Clin Anal Toxicol & Food Sci, Sch Pharmaceut Sci Ribeirao Preto FCFRP, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Dept Chem, Fac Philosophy Sci & Letters Ribeirao Preto FFCLR, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, LITEC, Dept Pharm, Sch Pharmaceut Sci, Ave Prof Lineu Prestes 580, Bloco 13, BR-05508000 Sao Paulo, SP - Brazil

^[5] Univ East Anglia, Sch Pharm, Norwich, Norfolk - England

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; v. 157, p. 657-664, SEP 5 2018.
• Citações Web of Science: 3

Resumo

It is known that aziridines and nitrogen mustards exert their biological activities, especially in chemotherapy, via DNA alkylation. The studied scaffold, 2-phenyl-1-aziridine, provides a distinct conformation compared to commonly used aziridines, and therefore, leads to a change in high-strained ring reactivity towards biological nucleophiles, such as DNA. The above series of compounds was tested in three breast cell lines: MCF-10, a healthy cell; MCF-7, a hormone responsive cancer cell; and MDA-MB-231, a triple negative breast cancer cell. Both aziridines and their precursors, beta-amino alcohols, showed activity towards these cells, and some of the compounds showed higher selectivity index than cisplatin, the drug used as control. When the type of cell death was investigated, the synthesized compounds demonstrated higher apoptosis and lower necrosis rates than cisplatin, and when the mechanism of action was studied, the compounds were shown to interact with DNA via its minor groove instead of alkylation or intercalation. (C) 2018 Elsevier Masson SAS. All rights reserved. (AU)

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