ABSTRACT
This review will discuss the contributions of marine natural molecules, a source only recently found to have pharmaceutical prospects, to the development of anticancer drugs. Of the seven clinically utilized compounds with a marine origin, four are used for the treatment of cancer. The development of these drugs has afforded valuable knowledge and crucial insights to meet the most common challenges in this endeavor, such as toxicity and supply. In this context, the development of these compounds will be discussed herein to illustrate, with successful examples provided by cytarabine, trabectedin, eribulin and brentuximab vedotin, the steps involved in this process as well as the scientific advances and technological innovation potential associated with developing a new drug from marine resources.
Subject(s)
Biotechnology/methods , Aquatic Organisms/chemistry , Drug Development/methods , Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Oceans and Seas , Immunoconjugates/therapeutic use , Immunoconjugates/pharmacology , Immunoconjugates/chemistry , Cytarabine/chemistry , Drug Discovery , Trabectedin/chemistry , Furans/chemistry , Brentuximab Vedotin , Ketones/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistryABSTRACT
Abstract Methanolic extracts of the Brazilian endemic ascidian Eudistoma vannamei have been extensively studied for their cytotoxic activity against several human cancer cell lines. Previous work reported the occurrence of purine derivatives and staurosporine alkaloids as the major nitrogen-containing compounds. In this study, we report the occurrence of three pyrimidine alkaloids in addition to cholesterol, sitosterol and stigmasterol.
ABSTRACT
Eudistoma vannamei (Millar, 1977) é uma ascídia endêmica do litoral do Nordeste brasileiro, largamente encontrado nas praias rochosas do estado do Ceará. Previamente, o extrato bruto apresentou um interessante perfil em termos de bioatividade. O fracionamento bioguiado identificou uma mistura 1:1 altamente citotóxica, contendo dois derivados inéditos de estaurosporina, 2-hidroxi-7-oxoestaurosporina (I) e 3-hidroxi-7-oxoestaurosporina (II). IC50 para I/II e estaurosporina (STP) foram obtidas após 72h de incubação com diversas linguagens de células tumorais, utilizando-se o ensaio do MTT, e em linfócitos humanos normais, através do ensaio de AlamarBlue. I/II superou a citotoxicidade de STP em 7 vezes, em média, para as células tumorais, ao passo que mostrou-se tão ativa quanto frente as células normais. Uma análise cinética sobre a progressão de ciclo celular, ativação de resposta a dano e vias de reparo de DNA, e indução de apoptose de células HL-60 (leucemia) foi conduzida com 40 ou 80ng/mL I/II e acessada por citometria de fluxo e western blotting...