Synthesis, biological evaluation and virtual screening of some acridone derivatives as potential anticancer agents

摘要

Eleven novel acridone derivatives were synthesized and evaluated for their anticancer activity against 60 human cancer cell lines. Five compounds 8b, 8d, 8g, 8h, and 8k displayed very good in vitro antiproliferative activities well over 95% of the panels. The most active compound is 8k (5, 7-dibromo-3-phenyl-3,4-dihydroacridin-1 (2H)-one). In addition, 8k was the most sensitive agent in all 9 panels starting with prostate (0.075 mu m), leukemia (0.116 mu m), non-small cell lung cancer (0.164 mu m), colon cancer (0.193 mu m), CNS cancer (0.264 mu m), melanoma (0.317 mu m), renal cancer (0.403 mu m), ovarian cancer (0.410 mu m), and breast cancer (0.608 mu m). Virtual screening studies also revealed that nine of the eleven compounds formed good binding interaction with the active site ATPase domain of human topoisomerase II alpha (PDB: 1zxm). All nine derivatives exhibited binding affinities that ranged in values from -8.5 to -7.9 kcal/mol, indicating that they could be catalytic inhibitors of the nuclear enzyme, topoisomerase.