Interaction between anticancer drug bendamustine and calf thymus DNA with spectroscopy at the single-molecule level

Abstract

Bendamustine (BENDA) has both alkylating and purinergic antitumor activities and remains effective in some cancers that have developed drug resistance, and there are few studies on the interaction mechanism of BENDA with DNA. In this paper, the interaction mechanism between BENDA and calf thymus DNA (ctDNA) was systematically investigated at the single molecular level, mainly by using ultraviolet-visible spectroscopy (UV-vis), Confocal Raman spectroscopy, and molecular docking. In UV-vis absorption spectroscopy experiments, the effects of ctDNA solution concentration, temperature, time and Na+ ions on the spectral production were investigated, respectively, and the experimental results showed that the interaction mode between BENDA and ctDNA was external bonding, i.e., groove binding and electrostatic binding. In addition, the disappearance and shift of the corresponding characteristic peaks in the Raman peaks indicate that BENDA interacts mainly with the phosphate backbone and base G of the ctDNA molecule, and causes some shifts in other bases and deoxyribose. Molecular docking simulations show that BENDA binds in the minor groove region of DNA and that the N and O atoms in the BENDA structure form intermolecular hydrogen bonds with base G, respectively. The results of this paper help to understand the mechanism of action of anti-cancer drugs and provide some reference for the development of new drugs with less toxic side effects.

Structural Insight into Groove Binding of Yohimbine with Calf Thymus DNA: A Spectroscopic, Calorimetric, and Computational Approach

“…To comprehend the origin of such molecular forces governing the binding process, salt-dependent fluorescence studies were carried out. Together with van’t Hoff analysis carried out in fluorescence at five varying concentrations of salt, it also reveals information on the characteristics of the interaction and the impact of salt content on the binding. ,, Around the double helix of DNA, cations remain available, forming counterions, and ligands attempt to release these cations to neutralize the phosphate backbone. Both mechanisms are thermodynamically related.…”

“…The hydrogen-bonding properties, electrostatic potential, steric requirements, hydration, hydrophobicity, and microenvironmental polarity of these grooves differ. , Due to steric effects, minor groove binders prefer AT-rich sequences to GC-rich sequences . Another important class of substances with broad-spectrum antibacterial, antiviral, anticancer, and antiprotozoal activity is nonintercalative DNA binding ligands, which exhibit various levels of sequence selectivity for binding to the DNA minor groove region. , Netropsin, distamin A, and Hoechst 33258 are some of the widely studied minor groove binding molecules that are known to attach to minor groove regions of the DNA upon AT specificity causing the minor grooves to widen. , Indole is one of the essential components found in the structure of alkaloids and several important biological molecules, including tryptophan, tryptamine, Hoechst 33258, serotonin, and gramine. They are also present in natural bioactive compounds like harmane, harmine, vinblastine, vincristine, and others. , Numerous molecules have been extensively utilized in pharmaceutical formulation. , It becomes evident that the indole ring is important for the molecules to interact with their biological receptors.…”

“…9 Another important class of substances with broadspectrum antibacterial, antiviral, anticancer, and antiprotozoal activity is nonintercalative DNA binding ligands, which exhibit various levels of sequence selectivity for binding to the DNA minor groove region. 10,11 Netropsin, distamin A, and Hoechst 33258 are some of the widely studied minor groove binding molecules that are known to attach to minor groove regions of the DNA upon AT specificity causing the minor grooves to widen. 12,13 Indole is one of the essential components found in the structure of alkaloids 14 and several important biological molecules, including tryptophan, tryptamine, Hoechst 33258, serotonin, and gramine.…”

Studying the Interaction between Bendamustine and DNA Molecule with SERS Based on AuNPs/ZnCl2/NpAA Solid-State Substrate

“…Only when both the hypochromic or hyperchromic effect and the obvious red shift appeared simultaneously, we considered the drug molecule and ctDNA as intercalative binding. From this, we can conclude that the interaction mechanism between BENDA and ctDNA is mainly groove binding in our series of experiments [40]. To have a further understanding of the binding strength of BENDA and ctDNA [41], we obtained Figure 8b based on the UV-vis spectral data at 232 nm in Figure 8a by a linear fit to Equation (2):…”