Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity
AbstractCancer 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
Share & Cite This Article
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.
Gonçalves AMMN, De Lima AB, Da Silva Barbosa MC, De Camargos LF, De Oliveira JT, De Souza Barbosa C, Villar JAFP, Costa AC, Silva IVG, Silva LM, De Pilla Varotti F, Dos Santos FV, Viana GHR. Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity. Marine Drugs. 2014; 12(8):4361-4378.Chicago/Turabian Style
Gonçalves, Alessandra M.M.N.; De Lima, Aline B.; Da Silva Barbosa, Maria C.; De Camargos, Luiz F.; De Oliveira, Júlia T.; De Souza Barbosa, Camila; Villar, José A.F.P.; Costa, André C.; Silva, Isabella V.G.; Silva, Luciana M.; De Pilla Varotti, Fernando; Dos Santos, Fabio V.; Viana, Gustavo H.R. 2014. "Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity." Mar. Drugs 12, no. 8: 4361-4378.