A Focused Library of NO-Donor Compounds with Potent Antiproliferative Activity Based on Green Multicomponent Reactions
Cancer is the second leading cause of death worldwide. Herein, a strategy to quickly and efficiently identify novel lead compounds to develop anticancer agents, using green multicomponent reactions followed by antiproliferative activity and structure–activity relationship studies, is described. A se...
| Autores: | , , , , , , , , , |
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| Formato: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2019 |
| País: | España |
| Recursos: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/193160 |
| Acesso em linha: | http://hdl.handle.net/10261/193160 |
| Access Level: | acceso abierto |
| Palavra-chave: | Green chemistry Solvent-free Multicomponent reactions Microwave-assisted synthesis Antiproliferative agents |
| Resumo: | Cancer is the second leading cause of death worldwide. Herein, a strategy to quickly and efficiently identify novel lead compounds to develop anticancer agents, using green multicomponent reactions followed by antiproliferative activity and structure–activity relationship studies, is described. A second-generation focused library of nitric oxide-releasing compounds was prepared by microwave-assisted Passerini and Ugi reactions. Nearly all compounds displayed potent antiproliferative activities against a panel of human solid tumor cell lines, with 1-phenyl-1-[(tert-butylamino)carbonyl]methyl 3-[(3-phenylsulfonyl-[1,2,5]oxadiazol-4-yl N-oxide)oxy]benzoate (4 k) and N-[1-(tert-butylaminocarbonyl)-1-phenylmethyl]-N-(4-methylphenyl)-3-(3-phenylsulfonyl-[1,2,5]oxadiazol-4-yl N-oxide)oxyphenyl carboxamide (6 d) exhibiting the strongest activity on SW1573 lung cell line (GI=110 and 21 nm) with selectivity indices of 70 and 470, respectively. Preliminary mechanistic studies suggest a relationship between NO release and antiproliferative activity. Our strategy allowed the rapid identification of at least two molecules as future candidates for the development of potent antitumor drugs. |
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