Literature DB >> 26526834

Cunninghamella Biotransformation--Similarities to Human Drug Metabolism and Its Relevance for the Drug Discovery Process.

Kamil Piska, Dorota Żelaszczyk, Marek Jamrozik, Paulina Kubowicz-Kwaśny, Elżbieta Pękala1.   

Abstract

BACKGROUND: Studies of drug metabolism are one of the most significant issues in the process of drug development, its introduction to the market and also in treatment. Even the most promising molecule may show undesirable metabolic properties that would disqualify it as a potential drug. Therefore, such studies are conducted in the early phases of drug discovery and development process. Cunninghamella is a filamentous fungus known for its catalytic properties, which mimics mammalian drug metabolism. It has been proven that C. elegans carries at least one gene coding for a CYP enzyme closely related to the CYP51 family. The transformation profile of xenobiotics in Cunninghamella spp. spans a number of reactions catalyzed by different mammalian CYP isoforms.
OBJECTIVE: This paper presents detailed data on similar biotransformation drug products in humans and Cunninghamella spp. and covers the most important aspects of preparative biosynthesis of metabolites, since this model allows to obtain metabolites in sufficient quantities to conduct the further detailed investigations, as quantification, structure analysis and pharmacological activity and toxicity testing.
CONCLUSION: The metabolic activity of three mostly used Cunninghamella species in obtaining hydroxylated, dealkylated and oxidated metabolites of different drugs confirmed its convergence with human biotransformation. Though it cannot replace the standard methods, it can provide support in the field of biotransformation and identifying metabolic soft spots of new chemicals and in predicting possible metabolic pathways. Another aspect is the biosynthesis of metabolites. In this respect, techniques using Cunninghamella spp. seem to be competitive to the chemical methods currently used.

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Year:  2016        PMID: 26526834     DOI: 10.2174/1389200216666151103115817

Source DB:  PubMed          Journal:  Curr Drug Metab        ISSN: 1389-2002            Impact factor:   3.731


  7 in total

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2.  In Vitro Biotransformation, Safety, and Chemopreventive Action of Novel 8-Methoxy-Purine-2,6-Dione Derivatives.

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3.  Biotransformation of bromhexine by Cunninghamella elegans, C. echinulata and C. blakesleeana.

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4.  Nitroreduction of flutamide by Cunninghamella elegans NADPH: Cytochrome P450 reductase.

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5.  Characterization of the global metabolic profile of liquiritin in rat plasma, urine, bile and feces based on UHPLC-FT-ICR MS.

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6.  The downregulated drug-metabolism related ALDH6A1 serves as predictor for prognosis and therapeutic immune response in gastric cancer.

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7.  Cunninghamella spp. produce mammalian-equivalent metabolites from fluorinated pyrethroid pesticides.

Authors:  Mohd Faheem Khan; Cormac D Murphy
Journal:  AMB Express       Date:  2021-07-08       Impact factor: 3.298

  7 in total

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