Title:Design and Discovery of Novel Quinoxaline Derivatives as Dual DNA Intercalators and Topoisomerase II Inhibitors
VOLUME: 18 ISSUE: 2
Author(s):Ibrahim H. Eissa, Abeer M. El-Naggar*, Nour E.A. Abd El-Sattar and Ahmed S. A. Youssef
Affiliation:Pharmaceutical Chemistry department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, 11884, Chemistry Department, Faculty of science, Ain Shams University, Abbassia, Cairo, 11566, Chemistry Department, Faculty of science, Ain Shams University, Abbassia, Cairo, 11566, Chemistry Department, Faculty of science, Ain Shams University, Abbassia, Cairo, 11566
Keywords:Anti-cancer, topoisomerase II, DNA intercalators, quinoxaline, docking.
Abstract:Backgroun/Methods: In attempt to develop new potent anti-tumor agents, a series of quinoxaline
derivatives was designed and synthesized. The novel compounds were tested in vitro for their anti-proliferative
activities against HePG-2, MCF-7 and HCT-116 cell lines. Additionally, DNA binding affinities as well as
DNA-top II inhibitory activities of the synthesized compounds were investigated as potential mechanism for
anticancer activity. Compounds 13, 15, 16 and 19 exhibited good cytotoxicity activities against the three cell
lines (IC50 ranging from 7.6 to 32.4 µM) comparable to that of doxorubicin (IC50 = 9.8 µM).
Results: Interestingly, the results of DNA binding and DNA-top II inhibition assays were in agreement with
those of the cytotoxicity tests, where the most potent anticancer compounds showed good DNA binding affinities
(IC50 ranging from 25.1 to 32.4 µM) and DNA-top II inhibitory activities (IC50 ranging from 6.4 to 15.3
µM) comparable to those of doxorubicin (IC50 = 28.1 and 3.8 μM, respectively). Furthermore, molecular
docking studies were carried out for the new compounds in order to investigate their binding pattern with the
prospective target, DNA-top II complex (PDB-code: 3qx3).
