Síntese de derivados 2,3-diino-1,4-naftoquinonas usando a reação de Sonogashira e avaliação da atividade citotóxica

• Autor(a) principal: SILVA, Mauro Gomes da
• Data de Publicação: 2012
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UFRPE
• Texto Completo: http://www.tede2.ufrpe.br:8080/tede2/handle/tede2/6364
• topic: Síntese orgânica; Naftoquinona; Sonogashira; Antitumoral; Cicloaromatização de Bergman; Organic synthesis; Naphthoquinone; Antitumor; Bergman cycloaromatization; Química; CIENCIAS EXATAS E DA TERRA::QUIMICA

In the present study ten 2,3-diyne-1,4-naphthoquinone derivatives were synthesized by Sonogashira coupling reaction between the 2,3-dibromo-1,4- naphthoquinone and several functionalized terminal alkynes using a catalytic complex of palladium (II) and CuI. Alkynes are among phenylacetylene, 1-ethyl-4- methoxybenzene, 2-methyl-3-butyn-2-ol, 1-ethynyl-1-cyclohexanol, 4-pentyn-2-ol, 4- pentyn-1-ol, 1-pentyne, 1-hexyne, 1-octyne and 1-decyne. The yields of products obtained ranged 15 to 55%. The enediynes having hydroxyl groups, in their structures such as 2,3-di(3-hydroxy-3-methylbut-1-yn-1-yl)-, 2,3-di[(1- hydroxycyclohexyl)ethynyl]- and 2,3-di(5-hydroxypent-1-yl)-1,4-naphthoquinone were subjected to acetylation reaction using acetic anhydride and montmorillonite clay K- 10 under sonication, thereby obtaining three new enediyne derivatives with yields ranging from 56 to 71%. The compounds were all characterized by 1H NMR and 13C NMR spectra, IR and MS-LC. These compounds containing the 1,4-naphthoquinone nucleus and acetylenic substituents in the quinonoid ring form a enediyne system (Z-3-ene-1,5-diyne) highly reactive, possibly subject to Bergman cycloaromatization, with potential antitumor activity. The enediynes underwent evaluation of the cytotoxic potential against three tumor cell lines, OVCAR-8 (ovarian adenocarcinoma - human), PC-3M (metastatic prostate cancer - human), NCI-H358M (bronchoalveolar lung carcinoma - human), presenting, in general, satisfactory results for inhibition of cell growth. The compound 2,3-di(3-hydroxy-3-methylbut-1-yn-yl)-1,4-naphthoquinone where said among the substances analyzed by presenting a lower IC50 (˂ 2 μg/mL) for three cell lines tested, which is characterized as a potent cytotoxic agent.