title: Synthesis and biological evaluation of novel 3-alkylpyridine marine alkaloid analogs with promising anticancer activity.
abstract: Cancer continues to be one of the most important health problems worldwide, and the identification of novel drugs and treatments to address this disease is urgent. During recent years, marine organisms have proven to be a promising source of new compounds with action against tumoral cell lines. Here, we describe the synthesis and anticancer activity of eight new 3-alkylpyridine alkaloid (3-APA) analogs in four steps and with good yields. The key step for the synthesis of these compounds is a Williamson etherification under phase-transfer conditions. We investigated the influence of the length of the alkyl chain attached to position 3 of the pyridine ring on the cytotoxicity of these compounds. Biological assays demonstrated that compounds with an alkyl chain of ten carbon atoms (4c and 5c) were the most active against two tumoral cell lines: RKO-AS-45-1 and HeLa. Micronucleus and TUNEL assays showed that both compounds are mutagenic and induce apoptosis. In addition, Compound 5c altered the cellular actin cytoskeleton in RKO-AS-45-1 cells. The results suggest that Compounds 4c and 5c may be novel prototype anticancer agents.
authors.affiliation: Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, Brazil. alessandramirtes@gmail.com.
authors.forename: Alessandra Mirtes Marques Neves
authors.initials: AM
authors.lastname: Gonçalves
authors.affiliation: Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, Brazil. lima.alinebrito@gmail.com.
authors.forename: Aline Brito
authors.initials: AB
authors.lastname: de Lima
authors.affiliation: Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, Brazil. mariacristinaufsj@gmail.com.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: da Silva Barbosa
authors.affiliation: Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, Brazil. luizfcamargos@yahoo.com.br.
authors.forename: Luiz Fernando
authors.initials: LF
authors.lastname: de Camargos
authors.affiliation: Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, Brazil. julia_toliveira@hotmail.com.
authors.forename: Júlia Teixeira
authors.initials: JT
authors.lastname: de Oliveira
authors.affiliation: Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, Brazil. camilasbbqi@gmail.com.
authors.forename: Camila
authors.initials: C
authors.lastname: de Souza Barbosa
authors.affiliation: Laboratório de Síntese Orgânica, Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, Brazil. zevillar@hotmail.com.
authors.forename: José Augusto Ferreira Perez
authors.initials: JA
authors.lastname: Villar
authors.affiliation: Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, Brazil. andrecfisio@hotmail.com.
authors.forename: André Carvalho
authors.initials: AC
authors.lastname: Costa
authors.affiliation: Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, Brazil. isabellavianagomes@yahoo.com.br.
authors.forename: Isabella Viana Gomes da
authors.initials: IV
authors.lastname: Silva
authors.affiliation: Serviço de Biologia Celular (SBC), Fundação Ezequiel Dias, Rua Conde Pereira Carneiro, 80, Belo Horizonte, MG 30.510-010, Brazil. luciana.silva@funed.mg.gov.br.
authors.forename: Luciana Maria
authors.initials: LM
authors.lastname: Silva
authors.affiliation: Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, Brazil.
authors.forename: Fernando
authors.initials: F
authors.lastname: de Pilla Varotti
authors.affiliation: Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, Brazil. fabiosantos@ufsj.edu.br.
authors.forename: Fabio Vieira
authors.initials: FV
authors.lastname: dos Santos
authors.affiliation: Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, Brazil. viana@ufsj.edu.br.
authors.forename: Gustavo Henrique Ribeiro
authors.initials: GH
authors.lastname: Viana
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D011725:Pyridines; C023666:pyridine
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