Design, synthesis and biological evaluation of new β-carboline-bisindole compounds as DNA binding, photocleavage agents and topoisomerase I inhibitors
Abstract A series of new β-carboline-bisindole compounds were designed, synthesized and evaluated for their antiproliferative activity against human cancer cell lines, such as A549 (lung cancer), DU-145 (prostate cancer), HeLa (cervical cancer) and MCF-7 (breast cancer). All the compounds exhibited considerable antiproliferative activity. Among them, compounds 7g and 7r exhibited significant antiproliferative activity against DU-145 cells with IC 50 values 1.86 and 1.80 μM respectively. Further, these compounds effectively inhibit DNA topoisomerase I activity and can also cleave the pBR322 plasmid upon irradiation with UV light. In addition, Annexin V-FITC assay suggested that these compounds induced apoptosis in DU- 145 cell line (prostate cancer). To know the binding mode of these compounds with DNA, spectroscopic studies were also carried out. These new compounds were showing a unique mode of binding with DNA, both biophysical studies such as UV–Visible, fluorescence, circular dichroism and molecular docking studies revealed that the β-carboline-bisindole compounds exhibit combilexin type of interaction with DNA. Highlights The synthesized β-carboline-bisindoles were showed antiproliferative activity. Annexin Annexin V-FITC assay suggested that thesecompounds induce apoptotic cell deathV-FITC assay suggested that these compounds induce apoptotic cell death. These compounds inhibit topoisomerase I activity. Effectively cleave the pBR322 plasmid upon irradiation with UV light. Spectroscopic and molecular docking studies supported combilexin type of interaction with DNA. Graphical abstract [DISPLAY OMISSION]
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