DESIGN AND MOLECULAR DOCKING STUDIES OF QUINAZOLINE DERIVATIVES AS ANTIPROLIFERATION
ABSTRACT: Nowadays, a lot of
new active substances as anticancer agents have been developed. One of the
protein targets of anticancer is selective cyclooxygenase-2 (COX-2). Selective
COX-2 is the regulator of cell proliferation. Objective: In this research,
quinazoline derivatives were used to design the anticancer agent through a
selective COX-2 inhibition. The potential activity of quinazoline derivatives
could be increased by substitution in position 2 and 3 of quinazolinone.
Molecular docking of selective COX-2 inhibition was required to predict their
antiproliferation activity. Methods: The molecular docking of quinazoline
derivatives was carried out using Molegro Virtual Docker (MVD) Ver.5.5.
Twenty-one of quinazoline derivatives were docked into selective COX-2 with PDB
code 3LN1. The interaction was evaluated based on the re-ranked score
comparison between quinazoline derivatives with co-crystallized ligand CEL_682.
Celecoxib was used as the reference to this research. Results: The result
indicated that 18 of 21 quinazoline derivatives showed the approximately
re-ranked score -131.508 to -108.418 kcal/mol. Eight of these 18 new
quinazoline derivatives have re-ranked score better than Celecoxib.
Conclusions: In conclusion, 8 of the new quinazoline derivatives are feasible
to be synthesize and performed their in vitro evaluation.
KEYWORDS: quinazoline
derivative; molecular darling; selective COX-2; antipoliferation
Penulis: Anita Puspa Widiyana,
Galih Satrio Putra, Luthfi Ahmad Muchlashi, Mellany Ika Sulistyowaty, Tutuk
Budiati
Kode Jurnal: jpfarmasidd160764
