title: Synthesis of N-methylarylnitrones derived from alkyloxybenzaldehydes and antineoplastic effect on human cancer cell lines.
abstract: 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.
authors: Laboratório de Química Bioorgânica, IPPN, CCS, s H1027, Cidade Universitária, Universidade Federal do Rio de Janeiro, Brazil.
authors: Débora S S
authors: DS
authors: Costa
authors: Laboratório Imunologia Aplicada e Bioquímica de Proteínas e Produtos Naturais, IBRAG, Universidade do Estado do Rio de Janeiro, Brazil.
authors: Thiago
authors: T
authors: Martino
authors: Laboratório Imunologia Aplicada e Bioquímica de Proteínas e Produtos Naturais, IBRAG, Universidade do Estado do Rio de Janeiro, Brazil.
authors: Fernanda C
authors: FC
authors: Magalhães
authors: Laboratório Imunologia Aplicada e Bioquímica de Proteínas e Produtos Naturais, IBRAG, Universidade do Estado do Rio de Janeiro, Brazil.
authors: Graça
authors: G
authors: Justo
authors: Laboratório Imunologia Aplicada e Bioquímica de Proteínas e Produtos Naturais, IBRAG, Universidade do Estado do Rio de Janeiro, Brazil.
authors: Marsen G P
authors: MG
authors: Coelho
authors: Laboratório de Química Bioorgânica, IPPN, CCS, s H1027, Cidade Universitária, Universidade Federal do Rio de Janeiro, Brazil.
authors: Julio C F
authors: JC
authors: Barcellos
authors: Laboratório de Química Orgânica, Instituto de Química, Universidade do Estado do Rio de Janeiro, Brazil.
authors: Victor B
authors: VB
authors: Moura
authors: Laboratório de Química Bioorgânica, IPPN, CCS, s H1027, Cidade Universitária, Universidade Federal do Rio de Janeiro, Brazil.
authors: Paulo R R
authors: PR
authors: Costa
authors: Laboratório Imunologia Aplicada e Bioquímica de Proteínas e Produtos Naturais, IBRAG, Universidade do Estado do Rio de Janeiro, Brazil.
authors: Kátia C C
authors: KC
authors: Sabino
authors: Laboratório de Química Orgânica, Instituto de Química, Universidade do Estado do Rio de Janeiro, Brazil. Electronic address: ayres.dias@gmail.com.
authors: Ayres G
authors: AG
authors: Dias
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001547:Benzaldehydes / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020014:K562 Cells; D051379:Mice; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009589:Nitrogen Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001547:Benzaldehydes; D009589:Nitrogen Oxides; C015388:nitrones; D009569:Nitric Oxide
keywords: Apoptosis; Cancer; Leukemia; Nitrones; O-Isoprenylated derivatives; p21CIP1/WAF1/Sdi1