| Abstrak/Abstract |
Erlotinib, Afatinib, and WZ4002 are quinazoline derivative compounds and
classified as first, second, and third-generation EGFR inhibitor. All inhibitors have been
given directly to cancer patients for many years but find some resistance. These three
compounds are candidates as the lead compound in designing a new inhibitor. This work
aims to design a new potential quinazoline derivative as an EGFR inhibitor focused on the
molecular docking result of the lead compound. The research method was started in
building a pharmacophore model of the lead compound then used to design a new
potential inhibitor by employing the AutoDock 4.2 program. Molecular dynamics
simulation evaluates the interaction of all complexes using the Amber15 program. There
are three new potential compounds (A1, B1, and C1) whose hydrogen bond interaction
in the main catalytic area (Met769 residue). The Molecular Mechanics Generalized Born
Surface Area (MM-GBSA) binding energy calculation shows that B1 and C1 compounds
have lower binding energies than erlotinib as a positive control, which indicates that B1
and C1 are potential as EGFR inhibitor. |
