Glicosilação regiosseletiva da hesperetina catalisada por Cunninghamella echinulata ATCC 9244, em biorreator
Nenhuma Miniatura disponível
Data
2019-03-19
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Federal de Goiás
Resumo
Introduction: Hesperetina is a flavonoid, belongs to flavanones class, with several pharmacological
activities, the most cited being the antioxidant potential. However, it presents low solubility and
consequently low bioavailability, making it difficult to apply it in a systemic pharmaceutical
formulation. Glycosylation of hesperetin effectively modifies its pharmacokinetic properties,
increasing its antidiabetic, antitilipidemic activity and efficacy against helicobacter pylori.
Filamentous fungi are used in biotechnological processes to increase the activity of molecules,
being able to glycosylate, regio and stereoselective derivatives, with less cytotoxicity.
Cunninghamella belongs to the class of filamentous fungi capable of catalyzing glycosylation
reactions. With the demand of scale-up the production of bioactive compounds, bioreactors are a
promising strategy, providing a controlled environment. Aim: The objective of this work was to
scale-up the regioselective glycosylation of hesperetin catalyzed by Cunninghamella echinulata
9244 in a bioreactor, with pharmacological activities improved. Methods: Hesperetin was
incubated with the microorganism in PDSM medium on two scales, semi-preparative (100 mL)
and preparative (2 L). HPLC-MS was used to monitoring and the caracterization of the product
formed was confirmed by 1H13C NMR. Tests of anticancer and cytotoxicity were realized. Results
and Discussion: The glycosylation yield in the semi-preparative scale was 0.8%, while in the
preparative scale the result was 22.9%. The increase in yield can be explained by the automated
control of the main parameters such as pH and oxygenation. The ideal time for biosynthesis of the
glycosylated derivative in bioreactor was 72 hours. The purified product glycosylated was
identified by NMR in hesperetin 7-O-β-D-glucopyranoside, not exhibiting anticancer activity, but
with reduction of cytotoxicity, with IC 50 9.5 times lower than the starting compound. Conclusions:
Regioselective glycosylation of hespertin was performed in a single step in bioreactor, significantly
increasing the yield. The chromatographic procedure proposed by the HPLC-MS allowed a fast
and efficient identification and characterization of the derivative.
Descrição
Palavras-chave
Citação
CARVALHO, P. H. O. Glicosilação regiosseletiva da hesperetina catalisada por Cunninghamella echinulata ATCC 9244, em biorreator. 2019. 81 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2019.