| spelling |
Ricardo José Alveshttp://lattes.cnpq.br/4654274038915572Adilson David da SilvaLucas Lopardi FrancoEufranio Nunes da Silva JunioAlaide Braga de Oliveirahttp://lattes.cnpq.br/1802884634752842Raquel Geralda Isidório2023-05-19T13:00:22Z2023-05-19T13:00:22Z2022-03-28http://hdl.handle.net/1843/53635Naftoquinonas são substâncias amplamente distribuídas na natureza e que apresentam diversas atividades biológicas tais como antifúngica, antibacteriana, anti-inflamatória, antiplasmodial, tripanocida e antitumoral. Lapachol e lausona são representantes importantes dessa classe de substâncias bioativas. O interesse em suas atividades biológicas tem motivado a preparação de derivados e análogos sintéticos por grupos de pesquisa no mundo inteiro. Destarte, neste trabalho de tese, foi realizada a síntese, a partir de lausona (2-hidroxi-1,4-naftoquinona), de onze derivados inéditos, oito glicosiltriazóis e três derivados de orto-furanonaftoquinonas. Os glicosiltriazóis foram preparados a partir de reação de cicloadição [2 +3] entre glicosilazidas peracetiladas, derivadas de D-glicose, D-galactose, D-N-acetilglicosamina e L-fucose, e 3-C-propargilausona. A remoção dos grupos acetila forneceu os derivados desacetilados correspondentes. Para obtenção dos derivados de orto-naftoquinona, inicialmente a 3-C-alil-lausona foi convertida no derivado 2-metil-2,3-di-hidrofurano-1,2-naftoquinona que, por reação com N-bromosuccinimida forneceu o derivado 2-bromometilnafto[1,2-b]furano-4,5-diona. Este, por reação com azida de sódio forneceu a azida correspondente. Alternativamente, a 3-C-alillausona foi convertida no derivado 2-iodometil-2,3-di-hidrofurano-1,2-naftoquinona que foi submetido a uma série de reações químicas nas quais se observou isomerização da orto-naftoquinona de partida para a para-naftoquinona correspondente. Além dos derivados inéditos supracitados foram sintetizados 18 intermediários de naftoquinona, dentre os quais um derivado de O- e C-alilação simultânea de lausona, bem como um derivado 3,3-dialilado, provavelmente resultante de rearranjo de Claisen do produto O,C-dialquilado. Também foi obtida uma antraquinona durante reação de lausona com propanal, na síntese de 2-metilnafto[1,2-b]furano-4,5-diona. A atividade antiplasmodial, antifúngica, antibacteriana, leishmanicida e citotóxica contra algumas linhagens de células tumorais (B16-F10, C6, A549) de diversas substâncias obtidas ao longo deste trabalho foi avaliada, sendo que algumas substâncias apresentaram atividade na faixa micromolar baixa (CI50 menor que 5 µM) e mesmo submicromolar, reforçando a importância da classe das naftoquinonas como estruturas privilegiadas para o desenvolvimento de fármacos.The naphthoquinones are substances widely distributed in nature and are endowed with diverse biological activities, such as antifungal, antibacterial, anti-inflammatory, antiplasmodial, trypanocidal and antitumor. Lapachol and lawsone are important representatives of this class of bioactive substances. The interest in their biological activities has motivated the preparation of derivatives and synthetic analogues by research groups worldwide. Therefore, in this thesis work, was conducted the synthesis, starting from lawsone (2-hydroxy-1,4-naphthoquinone), of eleven new derivatives: eight glycosyltriazoles and three derivatives of ortho-furanonaphthoquinones. The glycosyltriazoles were prepared from a [2+3] cycloaddition reaction between peracetylated glycosyl azides, derived from D-glucose, D-galactose, D-N-acetylglucosamine and L-fucose, and 3-C-propargyl-lawsone. Removal of the acetyl groups provided the equivalent deacetylated derivatives. To obtain the orthonaphthoquinone derivatives, the 3-C-allyl-lawsone was initially converted into the 2-methyl2,3-dihydrofuran-1,2-naphthoquinone derivative, which, by reaction with N-Bromo succinimide, provided the 2-bromomethylnaphtho[1,2-b]furan-4,5-dione. The abovementioned, upon reaction with sodium azide, provided the corresponding azide. Alternatively, the 3-C-allyl-lawsone was converted into the 2-iodomethyl-2,3-dihydrofuran-1,2- naphthoquinone derivative, which was subjected to a series of chemical reactions in which isomerization of the starting ortho-naphthoquinone was observed for the corresponding paranaphthoquinone. In addition to the new derivatives, eighteen naphthoquinone intermediates were synthesized, including an O- and C-allyl derivative of lawsone, as well as a 3,3- dialylated derivative, probably resulting from the Claisen rearrangement of the O,Cdialkylated product. An anthraquinone was also obtained during the reaction of lawsone with propionaldehyde in the synthesis of 2-methylnaphtho[1,2-b]furan-4,5-dione. The antiplasmodial, antifungal, antibacterial, leishmanicidal and cytotoxic activity against some tumor cell lines (B16-F10, C6, A549) of several substances obtained during this work was evaluated and some substances showed activity in the low micromolar range (IC50 lower than 5 µM) and even submicromolar, reinforcing the importance of the naphthoquinone class as key structures for drug development.porUniversidade Federal de Minas GeraisPrograma de Pós-Graduação em Ciências FarmacêuticasUFMGBrasilFARMACIA - FACULDADE DE FARMACIAhttp://creativecommons.org/licenses/by-nc-nd/3.0/pt/info:eu-repo/semantics/openAccessNaftoquinonasSínteseAtividade antiplasmodialAtividade antitumoralAtividade antimicrobianaSíntese de derivados de naftoquinonas com potencial atividade biologica.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8811https://repositorio.ufmg.br/bitstream/1843/53635/4/license_rdfcfd6801dba008cb6adbd9838b81582abMD54LICENSElicense.txtlicense.txttext/plain; charset=utf-82118https://repositorio.ufmg.br/bitstream/1843/53635/5/license.txtcda590c95a0b51b4d15f60c9642ca272MD55ORIGINALtese final conforme ri.pdftese final conforme ri.pdfSíntese de derivados de naftoquinonas com potencial atividade biológicaapplication/pdf17378292https://repositorio.ufmg.br/bitstream/1843/53635/3/tese%20final%20conforme%20ri.pdfe4864df3049d318b63c1fbbc1beb723cMD531843/536352023-05-19 10:00:23.114oai:repositorio.ufmg.br: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ório InstitucionalPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-05-19T13:00:23Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
|