In vitro cytotoxcity and interaction of new steroidal oxadiazinanones with calf thymus DNA using molecular docking, gel electrophoresis and spectroscopic techniques

• Design and synthesis of new steroidal oxadiazinanones.
• DNA interaction was studied by biochemical and spectroscopic methods.
• Compound 6 depicted higher binding affinity with DNA.
• Compound 6 depicted promising anticancer activity.

Herein we report synthesis of new steroidal oxadiazinanones from steroidal ketones. After characterization by spectral and analytical data, the interaction studies of compounds (4–6) with DNA were carried out by UV–vis, fluorescence spectroscopy and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb; 1.8 × 104 M−1, 2.2 × 104 M−1 and 2.6 × 104 M−1, respectively, indicating the higher binding affinity of compound 6 towards DNA. Gel electrophoresis showed the concentration dependent cleavage activity of compound 6 alone or in presence of Cu (II) causes the nicking of supercoiled pBR322 and it seems to follow the mechanistic pathway involving generation of hydroxyl radicals that are responsible for initiating DNA strand scission. Molecular simulations suggest that compounds binds through minor groove of DNA. MTT assay depicted promising anticancer activity of compound 5 and 6 particularly against HL-60 and MCF-7. The apoptotic degradation of DNA was analyzed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). The results revealed that compound 6 has better prospectus to act as cancer chemotherapeutic candidate which warrants further in vivo anticancer investigations.

Herein the synthesis of new steroidal oxadiazinanones is reported. After characterization, DNA binding studies, anticancer activity and genotoxicity was carried out.Figure optionsDownload as PowerPoint slide