Design and evaluation of pyrimidine derivatives as potent inhibitors of ABCG2, a breast cancer resistance protein.

ABSTRACT: The protein ATP-binding cassette subfamily G member 2 (ABCG2) is one of the major factors behind multidrug resistance (MDR) in breast cancer. We performed three-dimensional quantitative structure-activity relationship (3D-QSAR) modelling, docking, and molecular dynamics (MD) simulation to design pyrimidine-based ABCG2 antagonists. The developed QSAR model (r ² = 0.92, q ² = 0.82, and good cross-validated r ² = 0.73) dictate requirement of electrostatic, and hydrophobic fields for modulating bioactivity. Based on this rationale, we designed and screened 1010 new compounds, among them 2 (ND-510 and ND-500) exhibit excellent drug-like features. Comparative molecular docking, MM/GBSA and ADMET profiles were determined to understand the inte

SUBMITTER: Ahmad S 

PROVIDER: S-EPMC9296744 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature