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Topoisomerase enzyme, since its discovery, has been a promising target for the discovery of anticancer agents. In our earlier study, we have designed and synthesized flexible 2,4,6-trisubstituted pyridine derivatives and studied their topoisomerase inhibitory activity and cytotoxicity against several human cancer cell lines. Further optimization of the flexible 2,4,6-trisubstituted pyridine derivatives led us to synthesize various rigid analogues. In continuation of the previously reported chromeno[4,3-b]pyridine derivatives, herein we have prepared eleven 2,4-diaryl-5H-chromeno[4,3-b]pyridine derivatives (Figure 1(b)). All compounds were evaluated for their topoisomerase I and II inhibitory activity and cytotoxicity against several human cancer cell lines. Prepared compounds contain rigid chromeno[4,3b]pyridine skeleton at one side of the central pyridine. Chromeno[4,3-b]pyridine and chromene skeleton were found to have a wide range of biological activities such as estrogen receptor β-selective ligand, TNF-α inhibition, and anti-inflammatory activity.

2,4-Diaryl-5H-chromeno [4,3-b]pyridines: Synthesis, Topoisomerase I and II Inhibitory Activity, and Cytotoxicity