Synthesis, characterization, biological evaluation and molecular docking of steroidal spirothiazolidinones

• The synthesis of a new series of steroidal spirothiazolidinones has been performed.
• The interaction of products with DNA has been studied.
• Apoptosis and nonenzymatic degradation of DNA have also been investigated.
• The new compounds were tested for in vitro cytotoxicity against Jurkat and PBMCs.
• The AChE inhibitor activities were evaluated by Ellman’s method.

The present work describes a convenient synthesis of steroidal spirothiazolidinone derivatives (3, 10–12) in a two-step process. All the newly synthesized compounds have been characterized by means of elemental analyses, IR, 1H NMR, 13C NMR and MS. Lipinski’s ‘Rule of Five’ analysis and biological score predicted higher intrinsic quality of the synthesized compounds and revealed that these compounds have good passive oral absorption. The DNA binding studies of the synthesized compounds with CT-DNA were carried out by UV–vis and fluorescence spectroscopy. The molecular docking study suggested electrostatic interaction between synthesized compounds and nucleotide base pairs. The antitumor activity was tested in vitro against human leukemia cancer cell (Jurkat) and blood peripheral mononuclear normal cell (PBMCs) lines by MTT method. In addition, apoptosis and nonenzymatic degradation of DNA have been investigated. The acetylcholinesterase (AChE) inhibitor activities of the derivatives were also evaluated using Ellman’s method. The present study has shown that steroidal spirothiazolidinone derivatives (3, 10–12) can be used as template to design more potent and selective cytotoxic and AChE inhibition agents through modification and derivatization.

A convenient synthesis of new series of steroidal spirothiazolidinones has been performed. After characterization, the interaction of the synthesized compounds with DNA was evaluated by UV–vis, fluorescence spectroscopy and docking studies. MTT assay has been performed to check the in vitro cytotoxicity of new compounds.Figure optionsDownload as PowerPoint slide