Journal of Biomolecular Research & Therapeutics

Abstract

In Vitro DNA-Binding, Cleavage Activity with pBR322, Molecular Docking and Antiproliferative Studies of Newly Synthesized Steroidal Imidazolidine Hybrids

Ayaz Mahmood Dar, Shamsuzzaman, Mir Shabeer Ahmad and Manzoor Ahmad Gatoo

New steroidal imidazolidine derivatives (7-9) were synthesized by reacting steroidal thiosemicarbazones (4-6) with ethyl-2-chloroacetate 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, luminescence spectroscopy, circular dichroism and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb; 2.07 � 104 M-1, 2.1 � 104 M?1 and 1.9 � 104 M?1, respectively indicating the higher binding affinity of compound 8 towards DNA. Gel electrophoresis demonstrated that the compound 8 show strong interaction with DNA and during its cleavage activity with pBR322 DNA, it seems to follow the mechanistic pathway, involving singlet oxygen and superoxide anion to generate ROS responsible for initiating DNA strand scission. The docking study suggested the intercalation of imidazolidine moiety of steroid derivative in minor groove of DNA. In MTT assay, compounds 7-9 revealed potential toxicity against different human cancer cells especially compound 8 against A549 cells. Genotoxicity of compounds (7-9) was checked by comet assay. In western blotting, the expressions of relevant apoptotic markers depicted an apoptosis by steroidal imidazolidines in A549 cells.