Aim and Objective: For the development of new class of anticancer agents, a series of
novel 2-amino-3-cyanopyridine derivatives were designed from virtual screening with Glide
program by setting Topoisomerase II as the target.
Materials and Methods: The top ranked ten molecules from the virtual screening were synthesized
by microwave assisted technique and investigated for their cytotoxic activity against MCF-7 and A-
549 cell lines by using sulforhodamine B assay method.
Results: The most active compound 2-amino-4-(3,5-dibromo-4-hydroxyphenyl)-6-(2,4-
dichlorophenyl) nicotinonitrile (CG-5) showed significant cytotoxic profile with (LC50 = 97.1, TGI =
29.9 and GI50 = <0.1 µM) in MCF-7 and (LC50= 93.0, TGI= 50.0 and GI50= <7 µM) in A-549 cell
lines. A molecular docking study was performed to explore the binding interaction of CG-5with the
active site of Topoisomerase II.
Conclusion: It can be concluded that halogen substituent pyridine ring was benefit for cytotoxicity.