Journal of Physical Chemistry & Biophysics
Open Access

Abstract

Comprehensive Comparative Analysis of the Morphological Changes in a 12-mer DNA Oligonucleotide upon Platination by Cisplatin, Oxaliplatin and BNP3029 (a Substituted Cyano ligand-based Platinum analogue) using Molecular Dynamics Simulation Studies

Pavankumar PNV, Ayala PY, Parker AR, Zhao M, Jair K, Chen X, Kochat H and Hausheer FH

Cisplatin is an important anti-cancer agent widely used in the clinic; however, it has several notable limitations. To develop novel platinum analogues, key characteristics were considered that may result in more effective platinum analogues. In this study, we present comprehensive molecular dynamics simulation studies using a 12-mer DNA (5’-CCTCTggTCTCC-3’, gg= the site of platination) oligonucleotide which was platinated with cisplatin (1), oxaliplatin_1R_2R (2), and BNP3029 (3, a novel substituted cyano platinum analogue, PtCl2[N≡C(CH2)3(C6H5)]2), and analyzed the large data output using the Kolmogorov-Smirnov statistical analyses. In summary, data indicated that BNP3029-DNA had less A-like DNA morphology in comparison to cisplatin-DNA and oxaliplatin-DNA thus maintaining a more B-like DNA form. BNP3029 demonstrated more potent cytotoxic activity, relative to cisplatin and oxaliplatin, in a variety of human cancer cell lines, including several platinum-resistant cell lines.