Phase II metabolites of etofesalamide in filamentous fungi1

Abstract

Aim: To study phase II metabolites of etofesalamide in filamentous fungi. Methods: Seven fungi were screened to transform etofesalamide. The metabolites of etofesalamide were assayed using liquid chromatography coupled to mass spectrometry. The major metabolite was subject to enzymatic hydrolysis to confirm its structure. Results: Etofesalamide was converted into two phase II metabolites: glucoside and riboside conjugates. Glucoside conjugate was the major product with a yield greater than 90%; no phase I metabolites were detected. Conclusion: Glucoside and riboside conjugations of etofesalamide in filamentous fungi differ from the phase II metabolism of glucuronidation in mammals.

Biotransformation of metoprolol by the fungus Cunninghamella blakesleeana

“…As shown in Figure 3, 5 of the metabolites were essentially similar to those obtained in mammalian metabolism studies, whereas 2 novel metabolites, N-desalkylmetoprolol and the glucoside conjugate of O-desmethylmetoprolol, were identified. It has been well recognized that conjugation is an important metabolic pathway of many compounds both in mammals and in microorganisms [16][17][18] . A glucoside conjugate was detected in the present study, which conformed to previous studies that the glucosidation of drugs can be formed by microbial models [10,18,19] .…”

“…It has been well recognized that conjugation is an important metabolic pathway of many compounds both in mammals and in microorganisms [16][17][18] . A glucoside conjugate was detected in the present study, which conformed to previous studies that the glucosidation of drugs can be formed by microbial models [10,18,19] . In humans, metoprolol was metabolized to O-desmethylmetoprolol and metoprolol acid or α-hydroxymetoprolol, depending on the cytochrome P450 oxidation phenotype.…”

Cardiovascular Effects of Snake Toxins: Cardiotoxicity and Cardioprotection

“…Despite the fact that the amino acid sequences of CTs are very similar [ 49 ], their biological activity can differ significantly [ 50 , 51 ]. Most studies have shown that CTs begin to act even at a concentration of less than 1 μM, initially causing an increase in contraction, followed by a decrease and a concomitant rise in the resting tension [ 9 , 52 , 53 ]. Comparison of various myocardial tissues showed that the effect of CTs on the ventricular tissue is more pronounced than that on the atria [ 54 , 55 ].…”

Structural elucidation of phase I and II metabolites of bupivacaine in horse urine and fungi of the Cunninghamella species using liquid chromatography/multi‐stage mass spectrometry

“…Several studies have investigated the biotransformation of drugs by fungi [11][12][13][14][15][16][17][18][19] and it has been shown that some of these organisms produce mammalian metabolites. [11,[14][15][16][17][18][19] Examples of metabolic transformations in Cunninghamella fungi are the phase I reactions hydroxylation, [14] epoxidation, [14] N-oxidation, [20] N-dealkylation, [15] O-demethylation, [15] and deamination, [15] as well as the phase II reactions glucuronic acid conjugation, [21] sulfate conjugation, [21] glucoside conjugation, [13] and riboside conjugation. [13] This fungal genus has been found to express either a cytochrome P450 [22] or a similar enzymatic system.…”

“…[11,[14][15][16][17][18][19] Examples of metabolic transformations in Cunninghamella fungi are the phase I reactions hydroxylation, [14] epoxidation, [14] N-oxidation, [20] N-dealkylation, [15] O-demethylation, [15] and deamination, [15] as well as the phase II reactions glucuronic acid conjugation, [21] sulfate conjugation, [21] glucoside conjugation, [13] and riboside conjugation. [13] This fungal genus has been found to express either a cytochrome P450 [22] or a similar enzymatic system. [23] Cytochrome P450 enzyme systems mediate the metabolism of many compounds in mammals [24] and thus Cunninghamella fungi can be used to mimic mammalian drug metabolism.…”