In Vitro DNA-Binding, Cleavage Activity with pBR322, Molecular Docking and Antiproliferative Studies of Newly Synthesized Steroidal Imidazolidine Hybrids
- *Corresponding Author:
- Ayaz Mahmood Dar
Department of Chemistry
Aligarh Muslim University
Aligarh 202 002, India
E-mail: [email protected]; [email protected]
Received date: July 06, 2015 Accepted date: October 05, 2015 Published date: October 12, 2015
Citation: Dar AM, Shamsuzzaman, Ahmad MS, Gatoo MA (2015) In Vitro DNABinding,Cleavage Activity with pbr322, Molecular Docking and Antiproliferative Studies of Newly Synthesized Steroidal Imidazolidine Hybrids. J Biomol Res Ther 4:131. doi:10.4172/2167-7956.1000131
Copyright: © 2015 Dar AM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.