Objective: To study the interaction between DNA and impurities 5-hydroxymethylfurfural (5-HMF), its dipolymer 5,5'-oxydimethylenebis (2-furfural) (OMBF), and its metabolite 5-sulfooxymethylfurfural (5-SMF), and to provide theoretical basis to the research of the mechanism of potential risk of DNA damage and genotoxicity. Methods: The possibility of DNA binding and its warning structure of genotoxic of 5-HMF, OMBF and 5-SMF were predicted by using QSAR models, then the interaction between the three impurities and calf thymus DNA (ctDNA) was determined by using an ultraviolet (UV) spectroscopy to evaluate the possible mode of action for the spectral changes, and the simulated docking of three impurities and double-stranded DNA were finally investigated by using a computational molecular docking technology, the interaction between the three impuirities and DNA was intuitively presented, and the stability of the binding of three impurities and DNA were compared. Results: The results predicted by four QSAR models showed that all three impurities had the ability to bind with DNA (structural alert: furan) and the plausibility to induce mutagenicity and carcinogenicity (structural alert: aldehyde). 5-HMF, OMBF and 5-SMF showed a hypochromic effect on the UV spectrum of ctDNA with the degree of 8.2%, 22.6% and 8.7%, respectively, and blue shift with distance of 1.2 nm, 3.5 nm, and 1.0 nm. It demonstrated that three impurities could interact with ctDNA in the form of minor groove binding, accompanied by a π-π interaction with base pairs. The results obtained from computer-aided molecular docking simulation illustrated that three impurities could bind in the minor groove of DNA, hydrogen bonds with the base pairs, and the π-π interaction with the base pairs were found on OMBF and 5-SMF. By comparing the average of interaction energies of small impurities and DNA indicated that OMBF was the strongest, and then was the 5-SMF and 5-HMF was the weakest. Conclusion: The above results show that, the three impurities are capable to interact with DNA to form produce van der Waals force (minor groove binding), hydrogen bonds and π-π interaction and all may form impurity DNA complexes with DNA in a non-covalent way, thus inducing some degree of damage to the structure of DNA. This exploratory research has been conducted on the possible interactions of 5-HMF, OMBF or 5-SMF with DNA, and the potential mechanisms of DNA damage and genotoxicity are explored form the molecular level, providing new insights into the research on the genotoxicity of small molecular weight impurities.
LIN Ni, ZHANG Jia-ning, LIU Li, JIN Hong-tao, WANG San-long, LIU Ying
. Study on the interaction between DNA and impurities 5-hydroxymethylfurfural and its dipolymer and metabolite using QSAR model, ultraviolet spectroscopy and molecular docking technique*[J]. Chinese Journal of Pharmaceutical Analysis, 2023
, 43(7)
: 1221
-1228
.
DOI: 10.16155/j.0254-1793.2023.07.16
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