Differential Interactions of Cytochrome P450 3A5 and 3A4 with Chemotherapeutic Agent-Vincristine: A Comparative Molecular Dynamics Study

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)

Volume 17, 14 Issues, 2017

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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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  • 27th of 59 in Chemistry, Medicinal

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Michelle Prudhomme
Institut de Chimie de Clermont-Ferrand
Université Clermont Auvergne

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Differential Interactions of Cytochrome P450 3A5 and 3A4 with Chemotherapeutic Agent-Vincristine: A Comparative Molecular Dynamics Study

Anti-Cancer Agents in Medicinal Chemistry, 15(4): 475-483.

Author(s): Nikhat Saba, Rajabrata Bhuyan, Suman Kumar Nandy and Alpana Seal.

Affiliation: Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India, PIN 741235.


The chemotherapeutic agent vincristine, used for treatment of acute lymphoblastic leukemia is metabolized preferentially by polymorphic cytochrome P450 3A5 (CYP3A5) with higher clearance rate than cytochrome P450 3A4 (CYP3A4). As a result, CYP3A5 expressers have a reduced amount of vincristine-induced peripheral neuropathy than non–expressers. We modeled the structure of CYP3A5 and its interaction with vincristine, compared with CYP3A4-vincristine complex using molecular docking and simulation studies. This relative study helped us to understand the molecular mechanisms behind the interaction at the atomic level through interaction energy, binding free energy, hydrogen bond and solvent accessible surface area analysis - giving an insight into the binding mode and the main residues involved in this particular interaction. Our results show that the interacting groups get closer in CYP3A5-vincristine complex due to different orientation of vincristine. This leads to higher binding affinity of vincristine towards CYP3A5 compared to CYP3A4 and explains the preferential metabolism of vincristine by CYP3A5. We believe that, the results of the current study will be helpful for future studies on structure-based drug design in this area.


cancer, Cytochrome P450 3A5, Cytochrome P450 3A4, neurotoxicity, vincristine, vincristine-cytochrome interaction.

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Article Details

Volume: 15
Issue Number: 4
First Page: 475
Last Page: 483
Page Count: 9
DOI: 10.2174/1871520615666150129213510
Price: $58
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