Synthesis, Docking and Density Functional Theory Approaches on 1,3-Bis-3-(4-Chlorophenyl)-2,3-Dihydroquinazolin-4(1H)-on-2-Thioxopropane toward the Discovery of Dual Kinase Inhibitor

Abstract

1,3-Bis-3-(4-chlorophenyl)-2,3-dihydroquinazolin-4(1H)-on-2-thioxopropane (C), a quinazoline derivative was synthesized and well-characterized in order to evaluate its potential to act as VEGFR-2 and Aurora kinase inhibitor. ¹H NMR, elemental analysis and FT-IR confirmed the structure of the synthesized compound (C). Since, VEGFR-2 plays a crucial role in angiogenesis, it is hence a significant pharmaceutical target for the development of anti-angiogenic agents. While on the other hand, AURKA is an enzyme that is believed to induce normal cell proliferation and is encoded with over-expression witnessed in various types of malignant cancers. The electrostatic potential and the molecular geometry of the conformers 1-3, was demonstrated by DFT calculations. The results of which, revealed that the syn conformer 3 was the most stable. The molecular docking studies gave a brief insight about the binding of the conformer 3, also suggesting its potential to act as dual inhibitor, that inhibits VEGFR-2 and Aurora kinase, thereby could play an important role in cancer inhibition.

Graphical Abstract

Keywords:

• Aurora kinase
• DFT
• Molecular docking
• quinazoline
• VEGFR-2

Acknowledgements

The authors (S. Parveen, M. Hagar, R. Alnoman and H. Ahmad) gratefully acknowledge the Deanship of Scientific Research, Taibah University for support of our research group (60299).

Conflict of interest

The authors declare no conflict of interest.

Additional information

Funding

This study was funded by Deanship of Research, Taibah University.