Details

Autor(en) / Beteiligte

• Costa, Débora S.S.
• Martino, Thiago
• Magalhães, Fernanda C.
• Justo, Graça
• Coelho, Marsen G.P.
• Barcellos, Julio C.F.
• Moura, Victor B.
• Costa, Paulo R.R.
• Sabino, Kátia C.C.
• Dias, Ayres G.

Titel

Synthesis of N-methylarylnitrones derived from alkyloxybenzaldehydes and antineoplastic effect on human cancer cell lines

Ist Teil von

• Bioorganic & medicinal chemistry, 2015-05, Vol.23 (9), p.2053-2061

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• [Display omitted] New O-isoprenylated-N-methylarylnitrones derived from isomeric o, m and p-hydroxybenzaldehydes have been prepared and the antineoplastic effects on human cancer cell lines were evaluated. The O-geranylated nitrone LQB-278 (1b) and its isomers 2b and 3b inhibited the NO production, but the anti-leukemic activity was drastically dependent on nitrone isomer, with the 1b being the most effective one (IC50 of 6.7μM) on Jurkat leukemia cell, by MTT assay. In addition, 1b up-regulated p21CIP1/WAF1/Sdi1 protein expression (flow cytometry), a cell cycle inhibitor, reduced cell growth, and induced DNA fragmentation (increased sub-G1 phase cells) and phosphatidylserine externalization in plasmatic membrane (increased annexin V positive cells). Finally, the 1b up-regulation of p21 expression and apoptosis induction seem to be the mechanisms by which it promotes its anti-leukemic effects, making this new molecular architecture a promising prototype for leukemia intervention.