Design and synthesis of β-carboline linked aryl sulfonyl piperazine derivatives: DNA topoisomerase II inhibition with DNA binding and apoptosis inducing ability

A series of new beta-carboline linked aryl sulfonyl piperazine congeners have been synthesized by coupling various beta-carboline acids with substituted aryl sulfonyl piperazines. Evaluation of their anticancer activity against a panel of human cancer cell lines such as colon (HT-29), breast (MDA-MB-231), bone osteosarcoma (MG-63), brain (U87 MG), prostate (PC- 3) and normal monkey kidney (Vero) cell line has been done. Among the series, compound 8ec and 8ed has shown most potent cytotoxicity with an IC50 values of 2.80 +/- 0.10 mu M and 0.59 +/- 0.28 mu M respectively against MG-63 cell line and also potent on other cell lines tested. Compounds 8ec and 8ed was found to inhibit Topo II that is confirmed by specific Topo II inhibition assay. DNA binding studies, cell cycle analysis, Annexin V study indicate that these compounds has potential anticancer activity. Molecular docking studies for compound 8ec and 8ed are incorporated to understand the nature of interaction with topoisomerase IIa and dsDNA.