Synthesis and molecular docking studies of some novel Schiff bases incorporating 6-butylquinolinedione moiety as potential topoisomerase IIß inhibitors.

ABSTRACT

A series of novel pyranoquinolinone-based Schiff's bases were designed and synthesized. They were evaluated for topoisomerase IIß (TOP2B) inhibitory activity, and cytotoxicity against breast cancer cell line (MCF-7) for the development of novel anticancer agents. A molecular docking study was employed to investigate their binding and functional properties as TOP2B inhibitors, using the Discovery Studio 2.5 software, where they showed very interesting ability to intercalate the DNA-topoisomerase complex. Compounds 2a, 2c and 2f showed high docking score values (82.36% -29.98 kcal mol-1 for compound 2a, 78.18% -26.98 kcal mol-1 for compound 2c and 78.65, -28.11 kcal mol-1 for compound 2f) and revealed the highest enzyme inhibition activity. The best hit compounds exhibited highly potent TOP2B inhibitors with submicromolar IC50 at 5 µM compared to the reference doxorubicin.