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Review Articles

Mechanistic studies on the drug metabolism and toxicity originating from cytochromes P450

, , , , &
Pages 366-394 | Received 23 Jan 2020, Accepted 02 May 2020, Published online: 09 Jul 2020
 

Abstract

Cytochromes P450 are oxidizing enzymes; a few families of cytochromes P450 are implicated in drug metabolism. These enzymatic reactions involve many processes including (i) prodrug to drug conversion, (ii) easy excretion of drug, (iii) generation of reactive metabolites, many of which cause toxicity. In this review, the fundamental biochemical mechanisms associated with the conversion of drugs into the useful or toxic metabolites have been discussed. The mechanisms can be established with the help of many experimental methods like mass spectral analysis, NMR and in vitro analysis etc. Computational methods provide detailed atomic level information, which is generally not available from experimental studies. Thus, the in silico efforts in elucidating the molecular mechanisms are complementary to the known experimental methods and are often clearer (especially in providing 3D information about the metabolites and their reactions). Quantum chemical methods and molecular docking become especially very useful. This review includes five case studies, which explain how the atomic level details were obtained to explore the reaction mechanisms of drug metabolism by cytochromes P450.

Acknowledgements

PVB thanks DBT Indo-German health informatics project for the financial support.

This article was developed on the basis the experience gained while teaching the topic ‘Advanced Topics in Drug Action,’ a course which PVB was teaching for the past 12 years. The authors AG, HS, GR and KJ are the current batch students of the same Ph.D. level course. CKJ carried out research on the topic as a Ph.D. student. The authors thank all the earlier students of this course MC830 at NIPER, SAS Nagar.

Disclosure statement

No potential conflict of interest was reported by the author(s).

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