DNA Interaction Studies and In Vitro Cytotoxicity of Newly Synthesized Steroidal Imidazolidinones

Abstract

New steroidal imidazolidinone derivatives (7-9) were synthesized after reacting steroidal thiosemicarbazones with oxalyl chloride in absolute ethanol. After characterization by spectral and analytical data, the interaction studies of compounds (7-9) with DNA were carried out by UV-vis, fluorescence spectroscopy, circular dichroism, molecular docking and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb; 2.31 × 10(4) M(-1), 2.57 × 10(4) M(-1) and 2.16 × 10(4) M(-1), respectively indicating the higher binding affinity of compound 8 towards DNA. Gel electrophoresis demonstrated that the compounds 7-9 show strong interaction during the cleavage activity with pBR322 DNA. The docking study suggested the intercalation of imidazolidinone moiety of steroid derivative in minor groove of DNA. During in vitro cytotoxicity, compounds 7-9 revealed potential toxicity against the different human cancer cells (MTT assay). Apoptotic degradation of DNA in presence of compounds 7-9 was analyzed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). FACS analysis shows that the compound 8 bring about cell cycle arrest at 7 μM concentration.

Synthesis, characterization and biological activities of two novel orthopalladated complexes: Interactions with DNA and bovine serum albumin, antitumour activity and molecular docking studies

“…The cytotoxic activity of the complexes can be due to the presence of N,N‐chelating ligands, which increase the solubility and introduce electrostatic interactions in the complexes . The electrostatic interaction of the complexes with DNA can induce deleterious effects on cell cycle and growth . Furthermore, the SI values were calculated by comparing the cytotoxic activity (IC 50 ) of the complexes against each cancer cell type with that of the normal cell line to evaluate the selective effect of the tested complexes against cancer cells .…”

Imidazolidinones Derivatives As Pioneering Anticancer Agents: Unraveling Insights Through synthesis And Structure‐Activity Exploration

“…Cell cycle arrest and apoptosis induction: Imidazolidinone induces cell cycle arrest and apoptosis in various cancer cells. The cell cycle is often associated with the modulation of key regulatory proteins involved in the cell cycle, such as cyclins and cyclin‐dependent kinases (CDKs) [44] . By interfering with the normal progression of the cell cycle, imidazolidinone can prevent cancer cells from dividing and proliferating, and apoptosis is a crucial mechanism for eliminating damaged or abnormal cells [45] .…”

Rationale design and synthesis of some novel imidazole linked thiazolidinone hybrid molecules as DNA minor groove binders

“…Metronidazole and nitrofurantoin for instance are commercial imidazole-based antibiotics which target DNA and modify its structure. Many other imidazole and thiazolidinone based molecules reported in literature have shown strong affinity towards DNA thereby inhibiting its function [20][21][22]. Encouraged by these reports, we decided to probe DNA as possible target for the synthesized molecules.…”