New Anticancer Theobromine Derivative Targeting EGFR^WT and EGFR^T790M: Design, Semi-Synthesis, In Silico, and In Vitro Anticancer Studies.

ABSTRACT: Based on the pharmacophoric features of EGFR inhibitors, a new semisynthetic theobromine-derived compound was designed to interact with the catalytic pocket of EGFR. Molecular docking against wild (EGFR^WT; PDB: 4HJO) and mutant (EGFR^T790M; PDB: 3W2O) types of EGFR-TK indicated that the designed theobromine derivative had the potential to bind to that pocket as an antiangiogenic inhibitor. The MD and MM-GBSA experiments identified the exact binding with optimum energy and dynamics. Additionally, the DFT calculations studied electrostatic potential, stability, and total electron density of the designed theobromine derivative. Both in silico ADMET and toxicity analyses demonstrated its general likeness and safety. We synthesized the designed theobromine derivative (compo

SUBMITTER: Elkaeed EB 

PROVIDER: S-EPMC9500845 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature