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1.
Bioorg Chem ; 86: 550-556, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30782573

RESUMEN

Regio and stereoselective activation of sp3 CH bonds remain one of the major advantages of biocatalysis over traditional chemocatalytic methods. Herein, we describe the oxy-functionalization of halimane diterpenoid 1 by whole cells of three filamentous fungi, aiming to obtain derivatives with desirable biological properties. After incubating 1 with Fusarium oxysporum, Myrothecium verrucaria, and Rhinocladiella similis at different concentrations and incubation times, four known (3, 5, 6, and 7) and three new (2, 4, and 8) halimane derivatives were obtained and characterized. F. oxysporum catalyzed the hydroxylation of positions C-2 (2) and C-7 (4), while R. similis simultaneously mediated the 2-oxo-functionalization and the hydration of 13,14-(CC)double bond belonging to an α,ß-unsaturated carbonyl system (8). Compounds 1-7 were non-cytotoxic against HCT-116 and MCF-7 cancer cell lines at tested concentrations. However, substrate 1 displayed moderate reduction ability against biofilm produced by Staphylococcus epidermidis ATCC35984 (84% at 1.6 mM), and this effect was retained to some extent by derivatives 4 and 7. These results emphasize the prominent potential of filamentous fungi associated with the microbiota of medicinal plants as versatile catalysts for singularly useful reactions through their complex enzymatic machinery, as well as the high susceptibility of halimane-diterpenoid substrates.


Asunto(s)
Antineoplásicos/metabolismo , Ascomicetos/metabolismo , Diterpenos/metabolismo , Fusarium/metabolismo , Hypocreales/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacología , Ascomicetos/citología , Biopelículas/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Diterpenos/química , Diterpenos/farmacología , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Fusarium/citología , Células HCT116 , Humanos , Hypocreales/citología , Células MCF-7 , Estructura Molecular , Oxidación-Reducción , Staphylococcus epidermidis/efectos de los fármacos , Relación Estructura-Actividad
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