Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2014-07-01
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| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1660-3397/12/8/4361 |
| _version_ | 1811183925554315264 |
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| author | Alessandra Mirtes Marques Neves Gonçalves Aline Brito de Lima Maria Cristina da Silva Barbosa Luiz Fernando de Camargos Júlia Teixeira de Oliveira Camila de Souza Barbosa José Augusto Ferreira Perez Villar André Carvalho Costa Isabella Viana Gomes da Silva Luciana Maria Silva Fernando de Pilla Varotti Fabio Vieira dos Santos Gustavo Henrique Ribeiro Viana |
| author_facet | Alessandra Mirtes Marques Neves Gonçalves Aline Brito de Lima Maria Cristina da Silva Barbosa Luiz Fernando de Camargos Júlia Teixeira de Oliveira Camila de Souza Barbosa José Augusto Ferreira Perez Villar André Carvalho Costa Isabella Viana Gomes da Silva Luciana Maria Silva Fernando de Pilla Varotti Fabio Vieira dos Santos Gustavo Henrique Ribeiro Viana |
| author_sort | Alessandra Mirtes Marques Neves Gonçalves |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T13:05:01Z |
| format | Article |
| id | doaj.art-66d71e056f16441ea56b1a73d6e09d5a |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T13:05:01Z |
| publishDate | 2014-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-66d71e056f16441ea56b1a73d6e09d5a2022-12-22T04:22:47ZengMDPI AGMarine Drugs1660-33972014-07-011284361437810.3390/md12084361md12084361Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer ActivityAlessandra Mirtes Marques Neves Gonçalves0Aline Brito de Lima1Maria Cristina da Silva Barbosa2Luiz Fernando de Camargos3Júlia Teixeira de Oliveira4Camila de Souza Barbosa5José Augusto Ferreira Perez Villar6André Carvalho Costa7Isabella Viana Gomes da Silva8Luciana Maria Silva9Fernando de Pilla Varotti10Fabio Vieira dos Santos11Gustavo Henrique Ribeiro Viana12Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, BrazilPesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, BrazilPesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, BrazilPesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, BrazilPesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, BrazilPesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, BrazilLaboratório de Síntese Orgânica, Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, BrazilPesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, BrazilPesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, BrazilServiço de Biologia Celular (SBC), Fundação Ezequiel Dias, Rua Conde Pereira Carneiro, 80, Belo Horizonte, MG 30.510-010, BrazilPesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, BrazilPesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, BrazilPesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35.501-296, BrazilCancer 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.http://www.mdpi.com/1660-3397/12/8/43613-alkylpyridine alkaloidscancermutagenicityapoptosis |
| spellingShingle | Alessandra Mirtes Marques Neves Gonçalves Aline Brito de Lima Maria Cristina da Silva Barbosa Luiz Fernando de Camargos Júlia Teixeira de Oliveira Camila de Souza Barbosa José Augusto Ferreira Perez Villar André Carvalho Costa Isabella Viana Gomes da Silva Luciana Maria Silva Fernando de Pilla Varotti Fabio Vieira dos Santos Gustavo Henrique Ribeiro Viana Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity Marine Drugs 3-alkylpyridine alkaloids cancer mutagenicity apoptosis |
| title | Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity |
| title_full | Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity |
| title_fullStr | Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity |
| title_full_unstemmed | Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity |
| title_short | Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity |
| title_sort | synthesis and biological evaluation of novel 3 alkylpyridine marine alkaloid analogs with promising anticancer activity |
| topic | 3-alkylpyridine alkaloids cancer mutagenicity apoptosis |
| url | http://www.mdpi.com/1660-3397/12/8/4361 |
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