Enantioselective biotransformation of propranolol to the active metabolite 4-hydroxypropranolol by endophytic fungi

Abstract

. do Café, s/n, 14040-903 Ribeirão Preto -SP, BrasilRecebido em 22/11/10; aceito em 18/3/11; publicado na web em 10/6/11The enantioselective biotransformation of propranolol (Prop) by the endophytic fungi Phomopsis sp., Glomerella cingulata, Penicillium crustosum, Chaetomium globosum and Aspergillus fumigatus was investigated by studying the kinetics of the aromatic hydroxylation reaction with the formation of 4-hydroxypropranolol (4-OH-Prop). Both Prop enantiomers were consumed by the fungi in the biotransformation process, but the 4-hydroxylation reaction yielded preferentially (-)-(S)-4-OH-Prop. The quantity of metabolites biosynthesized varied slightly among the evaluated endophytic fungi. These results show that all investigated endophytic fungi could be used as biosynthetic tools in biotransformation processes to obtain the enantiomers of 4-OH-Prop.

Gas‐phase fragmentation of protonated piplartine and its fungal metabolites using tandem mass spectrometry and computational chemistry

“…Fungal models have been extensively used because they are capable of carrying out chemo‐, regio‐ and stereospecific reactions similar to humans, with advantages of higher yields of metabolites, facilitating structural elucidation and providing standard compounds for in vivo studies . For instance, the endophytic fungus Penicillium crustosum VR4 is a microbial model to mimic human metabolism, as evidenced by the oxidative biotransformation of the drugs propranolol and thioridazine …”

“…[19][20][21] For instance, the endophytic fungus Penicillium crustosum VR4 is a microbial model to mimic human metabolism, as evidenced by the oxidative biotransformation of the drugs propranolol and thioridazine. [20,22] Mass spectrometry (MS) has been applied to identify metabolites produced during in vitro and in vivo metabolism studies. [23] Soft ionization sources, such as electrospray ionization (ESI) [24] and matrix-assisted laser desorption/ionization (MALDI) [25] coupled with tandem mass spectrometry (MS/MS) analysis, have contributed to the characterization and elucidation of metabolite structures in complex matrices.…”

Biotransformação da B-lapachona utilizando culturas microbianas: uma alternativa para estudos de metabolismo in vitro

“…Porém, com o procedimento de transformação microbiana da β-lapachona, esse fungo filamentoso não propiciou a obtenção de derivados com rendimento significativo, após sete dias de incubação. Esse fungo já foi utilizado em diversos processos de biotransformação de fármacos, principalmente em processos com exigência enantiosseletiva (CARRÃO et al, 2011;BORGES et al, 2011). Porém não se obteve êxito na biotransformação da Figura 59.…”