Synthesis of 3-(arylamino) quinazoline-2,4(1H,3H)-dione derivatives via TBHP/I2: Molecular docking, MD simulation, DFT, and pharmacological evaluation as MTH1 inhibitors.

ABSTRACT: A series of novel derivatives of 3-(arylamino) quinazoline-2,4(1H,3H)-dione were synthesized with moderate to good yields (20%-70%) using t-butyl hydroperoxide (TBHP) and iodine. Their efficacy against MutT homologue 1 (MTH1) was evaluated using in silico methods. Density functional theory (DFT) analysis, utilizing the B3LYP/6-311G (2df, p) basis set, indicated a promising reactivity profile for the synthesized compounds. The highest occupied molecular orbital (HOMO) regions associated with the phenylhydrazine group serve as sites for electron donation, functioning as electron-rich nucleophiles. Docking analysis with MTH1 enzymes revealed that all compounds exhibited docking scores ranging from -5.77 to -7.24, indicating favorable binding affinities. Among these, compound (3d), with an ene

SUBMITTER: Karim MG 

PROVIDER: S-EPMC12614599 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature