Synthesis of N-methylarylnitrones derived from alkyloxybenzaldehydes and antineoplastic effect on human cancer cell lines
| Autor: | Graça Justo, Paulo R. R. Costa, Marsen Garcia Pinto Coelho, Victor B. Moura, Julio C. F. Barcellos, Kátia Costa de Carvalho Sabino, Fernanda Cândido Magalhães, Ayres G. Dias, Débora S.S. Costa, Thiago Martino |
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| Rok vydání: | 2015 |
| Předmět: |
Clinical Biochemistry
Cell Pharmaceutical Science Antineoplastic Agents Apoptosis Nitric Oxide Biochemistry Jurkat cells Cell Line Mice Structure-Activity Relationship Annexin Drug Discovery medicine Animals Humans MTT assay Molecular Biology Cell Proliferation Dose-Response Relationship Drug Molecular Structure Chemistry Cell growth Cell Cycle Organic Chemistry Cell cycle Molecular biology medicine.anatomical_structure Benzaldehydes NIH 3T3 Cells Molecular Medicine DNA fragmentation Nitrogen Oxides Drug Screening Assays Antitumor K562 Cells |
| Zdroj: | Bioorganic & Medicinal Chemistry. 23:2053-2061 |
| ISSN: | 0968-0896 |
| Popis: | 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 6.7 μM) 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. |
| Databáze: | OpenAIRE |
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