New Potent Deuterated Methoxy of 4-Anilinoquinazoline Derivatives Targeting Eight Receptor Tyrosine Kinases: Synthesis, In Vitro, and In Silico Studies
نویسندگان
1 Doctoral Program of Chemistry, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung, 40132, Jawa Barat, Indonesia
2 Chemistry Study Program, Universitas Negeri Jakarta, Jakarta, 13220, Indonesia
3 Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Pakuan, Jl. Pakuan, Bogor, 16143, Jawa Barat, Indonesia
4 Organic Chemistry Division, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung, 40132, Jawa Barat, Indonesia
5 Organic Chemistry Division, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung, 40132, Jawa Barat, Indonesia
6 Organic Chemistry Division, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung, 40132, Jawa Barat, Indonesia
7 Organic Chemistry Division, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung, 40132, Jawa Barat, Indonesia
doi
10.48309/chemm.2026.553098.2022چکیده
Three 7-methoxyquinazoline derivatives were successfully synthesized 6-8. Among them, compound 7 is a new deuterated analog, while compound 8 is the deuterated version of a previously reported non-deuterated compound. The three compounds 6-8 were evaluated for their inhibitory activity against eight tyrosine kinase receptors (EGFR, HER2, HER4, IGF1R, InsR, VEGFR2, PDGFRα, and PDGFRβ). The results showed that compound 7 exhibited strong inhibition (>80% inhibition) against EGFR, HER2, and VEGFR2, while compound 8 showed strong inhibition against EGFR and moderate inhibition (40-60% inhibition) against HER2 and VEGFR2. The results of molecular docking using AutoDock showed that the deuterated methoxy of compound 7 provided a better inhibition constant value than the other compounds. Meanwhile, the results of visualization of the interaction of compounds 6-8 in the receptor showed that the quinazoline ring was positioned the active site like native ligand. Molecular dynamics simulations indicated that the molecular complexations between compounds 7 and receptors are likely to be stable in an aqueous environment. The ADMET prediction indicates that the deuterated compound is promising as a lead compound for further development as tyrosine kinase inhibitors.
