Comparison of catalytic and inhibitory properties in human drug-metabolizing cytochrome P450 3A4 and 3A5 for various compounds including endogenous steroid hormones and azole antifungals by molecular docking simulation

Niwa, Toshiyuki; Murayama, Norie; Imagawa, Yurie; Yamazaki, Hiroshi

doi:10.1016/j.dmpk.2016.10.164

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A polymorphism of CYP3A5 showed different reactivity towards several hypertensive drugs, thus affecting the blood pressure in the studied individuals [ 30 ]. Several studies have already used CYP3A5 as a potential target for the in silico assessment of potential molecules [ 31 , 32 , 33 , 34 ]. Hence, the above data and research findings substantiated that CYP3A5 is a crucial and validated drug target for cardiovascular and other diseases [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Potential Cytochrome P450 3A5 Inhibitors: An Extensive Virtual Screening through Molecular Docking, Negative Image-Based Screening, Machine Learning and Molecular Dynamics Simulation Studies

Islam¹,

Dudekula²,

Rallabandi³

et al. 2022

IJMS

View full text Add to dashboard Cite

Cytochrome P450 3A5 (CYP3A5) is one of the crucial CYP family members and has already proven to be an important drug target for cardiovascular diseases. In the current study, the PubChem database was screened through molecular docking and high-affinity molecules were adopted for further assessment. A negative image-based (NIB) model was used for a similarity search by considering the complementary shape and electrostatics of the target and small molecules. Further, the molecules were segregated into active and inactive groups through six machine learning (ML) matrices. The active molecules found in each ML model were used for in silico pharmacokinetics and toxicity assessments. A total of five molecules followed the acceptable pharmacokinetics and toxicity profiles. Several potential binding interactions between the proposed molecules and CYP3A5 were observed. The dynamic behavior of the selected molecules in the CYP3A5 was explored through a molecular dynamics (MD) simulation study. Several parameters obtained from the MD simulation trajectory explained the stability of the protein–ligand complexes in dynamic states. The high binding affinity of each molecule was revealed by the binding free energy calculation through the MM-GBSA methods. Therefore, it can be concluded that the proposed molecules might be potential CYP3A5 molecules for therapeutic application in cardiovascular diseases subjected to in vitro/in vivo validations.

show abstract