Molecular dynamics simulation study of DNA conformation changes caused by the dinuclear platinum(II) complexes with the bisphosphonate group

Chaoqun Li; Xiaojia Zhao; Fangqian Yin; Huimin Bi; Yan Wang

doi:10.1016/j.jinorgbio.2023.112179

Molecular dynamics simulation study of DNA conformation changes caused by the dinuclear platinum(II) complexes with the bisphosphonate group

J Inorg Biochem. 2023 Jun:243:112179. doi: 10.1016/j.jinorgbio.2023.112179. Epub 2023 Mar 17.

Authors

Chaoqun Li¹, Xiaojia Zhao², Fangqian Yin², Huimin Bi², Yan Wang³

Affiliations

¹ Hebei Key Laboratory of Heterocyclic Compounds, College of Chemistry, Chemical Engineering and Materials, Handan University, Handan 056005, Hebei province, China. Electronic address: lichaoqun@hdc.edu.cn.
² Hebei Key Laboratory of Heterocyclic Compounds, College of Chemistry, Chemical Engineering and Materials, Handan University, Handan 056005, Hebei province, China.
³ College of Chemistry, Beijing Normal University, 19# Xinjiekouwai Street, Beijing 100875, China.

PMID: 36989944
DOI: 10.1016/j.jinorgbio.2023.112179

Abstract

Bisphosphonate (BP) has been widely used as a bone-targeting group, and the BP-modified platinum(II) complexes have shown potential to as anticancer drugs against bone-related diseases, such as osteosarcoma. DNA conformation changes induced by the BP-modified dinuclear platinum(II) complexes have been investigated using molecular dynamics simulations. The results indicated that the BP-modified dinuclear platinum(II) complexes coordinated to DNA results in DNA structural distortions, including twisting, unwinding and bending. Furthermore, the rigidity of the bridging linkers in the BP-modified platinum(II) complex may induce more significant DNA structural distortions with same spans. The results provide the detail information of DNA conformational changes induced by the BP-modified platinum(II) complexes with different flexibility of bridging linkers, and are helpful for exploring novel platinum-based antitumor drugs.

Keywords: Bisphosphonate; Bridging linker; Conformation changes; DNA; Dinuclear platinum(II) complexes; Molecular dynamics simulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents* / chemistry
Antineoplastic Agents* / pharmacology
DNA / chemistry
Diphosphonates
Molecular Dynamics Simulation
Nucleic Acid Conformation
Platinum* / chemistry

Substances

Platinum
Diphosphonates
Antineoplastic Agents
DNA