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Mar. Drugs 2014, 12(8), 4361-4378; doi:10.3390/md12084361

Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity

1
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
2
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
3
Serviço de Biologia Celular (SBC), Fundação Ezequiel Dias, Rua Conde Pereira Carneiro, 80, Belo Horizonte, MG 30.510-010, Brazil
*
Authors to whom correspondence should be addressed.
Received: 24 April 2014 / Revised: 24 June 2014 / Accepted: 9 July 2014 / Published: 31 July 2014
(This article belongs to the Special Issue Alkaloid Analogs)
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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. View Full-Text
Keywords: 3-alkylpyridine alkaloids; cancer; mutagenicity; apoptosis 3-alkylpyridine alkaloids; cancer; mutagenicity; apoptosis
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MDPI and ACS Style

Gonçalves, A.M.M.N.; de Lima, A.B.; da Silva Barbosa, M.C.; de Camargos, L.F.; de Oliveira, J.T.; de Souza Barbosa, C.; Villar, J.A.F.P.; Costa, A.C.; Silva, I.V.G.; Silva, L.M.; de Pilla Varotti, F.; dos Santos, F.V.; Viana, G.H.R. Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity. Mar. Drugs 2014, 12, 4361-4378.

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