Aplicação de fungos filamentosos para S-oxidação do ácido 2-[4-(1,4-tiazinan-4-ilsulfonil) fenilcarbamoil] benzóico (LASSBio-596)

• Autor(a) principal: Cavaion, Juliana Camila Lopes
• Data de Publicação: 2012
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/3806
• topic: Microrganismos; Previsão in silico; LASSBio-596; Beauveria bassiana; S-oxidação; Sulfona; Microorganisms; In silico prediction; LASSBio-596; Beauveria bassiana; S-oxidation; Sulfone; CIENCIAS DA SAUDE::FARMACIA

Filamentous fungi have cytochrome P450 enzyme system similar to mammals whose application allows catalyze phase I oxidative reactions of metabolism. Obtaining functionalized derivatives by these microorganisms was the main purpose of this dissertation. Studies in silico to predict metabolism in the programs MetaPrint2D and SMARTCyp indicated S-oxidation, aromatic hydroxylation and dealkylation reactions, as the most likely S-oxidation in thiomorpholine ring of 2-[4-(1,4-thiazinan-4-ylsulfonyl)phenylcarbamoyl]benzoic acid (LASSBio-596). The filamentous fungi Absidia blakesleana ATCC 26617, Aspergillus candidus ATCC 1009, Beauveria bassiana ATCC 7159, Cunninghamella echinulata ATCC 9244, Cunninghamella echinulata ATCC 9245, Cunninghamella elegans ATCC 36112, Fusarium roseum ATCC 14717 and Streptomyces vendulae ATCC 8664 were used for biotransformation of LASSBio-596. In the reaction conditions applied, substrate dissolved in methanol with concentration of 0.25 mg/mL added to liquid culture medium PDSM and incubated at 27 °C with 200 rpm for 96 hours, the fungus Beauveria bassiana ATCC 7159 performed S-oxidation in the thiomorpholine ring resulting in sulfone derivative of LASSBio-596, called LaBioCon 214, yield of 5.84 %, and it was found the hydrolysis of amide reaction obtaining the compound 4-(thiomorpholinosulfonyl)aniline, LaBioCon 202, yield of 13.8 %. It was noted the solvent used affects the biotransformation process. The monitoring of the reactions and purification of the derivatives obtained were performed by high performance liquid chromatography with ultraviolet detector at 267 nm and preparative chromatography with column Microsorb 100-5 C18 (250 x 10 mm, 5 μm). Subsequently, sulfone derivative was obtained, called LaBioCon 223, by synthesis. Structural characterization was made by classical methods such as 1H NMR and mass spectrometry.