Assessment of molecular binding of Hoechst 33258 analogues into DNA using docking and MM/GBSA approach

Issar, Upasana; Kumari, Tripti; Kakkar, Rita

doi:10.1016/j.jocs.2015.05.003

Cited by 12 publications

(5 citation statements)

References 65 publications

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“…To perform the calculations, the DICKERSON-DREW B-DNA DODECAMER was obtained from the Protein Data Bank (PDB) with code 4C64 and resolution: 1.32 Å (Lercher et al, 2014). This DNA structure was chosen as the model according to previous studies (Haris et al, 2015;Issar et al, 2015). As mentioned previously, the dyes and their metabolites were entirely optimized at DFT level for the subsequent PM6 semi-empirical calculations with B-DNA.…”

Section: Lc-ms/ms Experimental Conditionsmentioning

confidence: 99%

Identification of biotransformation products of disperse dyes with rat liver microsomes by LC-MS/MS and theoretical studies with DNA: Structure-mutagenicity relationship using Salmonella/microsome assay

Franco

Silva

Oliveira³

et al. 2018

Science of The Total Environment

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Azo dyes are known as a group of substances with DNA damage potential that depend on the nature and number of azo groups connected to aromatic rings (benzene and naphthalene), chemical properties, e.g. solubility and reactive functional groups, which significantly affect their toxicological and ecological risks. In this paper, we used in vitro models to evaluate the metabolism of selected textile dyes: Disperse Red 73 (DR 73), Disperse Red 78 (DR 78) and Disperse Red 167 (DR 167). To evaluate the mutagenic potential of the textile dyes, the Salmonella mutagenicity assay (Ames test) with strains TA 98 and TA 100 in the presence and absence of the exogenous metabolic system (S9) was used. DR73 was considered the most mutagenic compound, inducing both replacement base pairs (TA 100) and also changing frameshift (TA 98) mutations that are reduced in the presence of the S9 mixture. Furthermore, we used rat liver microsomes in the same experimental conditions of the S9 mixture to metabolize the dyes and the resultant solutions were analyzed using a liquid chromatography coupled to a quadrupole linear ion trap mass spectrometry (LC-MS/MS) to investigate the metabolites formed by the in vitro biotransformation. Based on this experiment, we detected and identified two biotransformation products for each textile dye substrate analyzed. Furthermore, to evaluate the interaction and reactivity of these compounds with DNA, theoretical calculations were also carried out. The results showed that the chemical reaction occurred preferentially at the azo group and the nitro group, indicating that there was a reduction in these groups by the CYP P450 enzymes presented in the rat microsomal medium. Our results clearly demonstrated that the reduction of these dyes by biological systems is a great environmental concern due to increased genotoxicity for the body of living beings, especially for humans.

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Section: Lc-ms/ms Experimental Conditionsmentioning

confidence: 99%

Identification of biotransformation products of disperse dyes with rat liver microsomes by LC-MS/MS and theoretical studies with DNA: Structure-mutagenicity relationship using Salmonella/microsome assay

Franco

Silva

Oliveira³

et al. 2018

Science of The Total Environment

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“…H-bond analyses and SASA calculations were performed using the cpptraj utility of AMBER 19. The free energy difference between the complexed and native G-quadruplex RNA was calculated by using the MM_GBSA [molecular mechanics (MM), generalized Born (GB), surface area] module of AMBER 19. ,,, …”

Section: Methodsmentioning

confidence: 99%

“…The free energy difference between the complexed and native G-quadruplex RNA was calculated by using the MM_GBSA [molecular mechanics (MM), generalized Born (GB), surface area] module of AMBER 19. 43,44,54,55 Ligand Strain Energy Calculation. The strain energy is defined as the energy difference between the bound conformation of the complexed ligand and the unbound ligand in solvent (water).…”

Section: ■ Introductionmentioning

confidence: 99%

Theoretical Insight into the Library Screening Approach for Binding of Intermolecular G-Quadruplex RNA and Small Molecules through Docking and Molecular Dynamics Simulation Studies

2021

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The interactions of intermolecular G-quadruplex RNA and small molecules have been investigated by computational studies. Various anthraquinone, bisbenzimidazole, and carbazole–benzimidazole based ligands have shown a distinct preference to G-quadruplex structures as opposed to the corresponding duplex forms of DNA that were docked with telomeric G-quadruplex RNA. The comparative binding study of such ligands with G-quadruplex (G4) RNA showed higher binding affinities toward carbazole–benzimidazole ligands than those of the anthraquinone and bisbenzimidazole based ligands. A molecular dynamics simulation study was used to examine quadruplex–ligand interactions. Analysis of the binding free energy indicated the formation of the thermodynamically favorable RNA–ligand complex. The formation of several H-bonding interactions and the change of the solvent accessible surface area (SASA) also support the effective binding of the carbazole–benzimidazole ligands with G4 RNA structures. Thus, the library screening approach has assisted in getting a structure–activity relationship for the selected small molecules toward the G-quadruplex RNA binding, which can be applied in the targeting of G-quadruplex RNA medicated anticancer therapeutics.

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“…To perform the calculations, the DICKERSON-DREW B-DNA DODECAMER was obtained from the Protein Data Bank (PDB) with code 4C64 and resolution 1.32 Å (Lercher et al, 2014). This DNA structure was chosen as the model based on previously reported studies (Haris et al, 2015;Issar et al, 2015). The dyes and their metabolites were entirely optimized at DFT level for the subsequent PM6 semi-empirical affinity calculations with B-DNA.…”

Section: Semi-empirical and Quantum Calculationsmentioning

confidence: 99%

Biotransformation of disperse dyes using nitroreductase immobilized on magnetic particles modified with tosyl group: Identification of products by LC-MS-MS and theoretical studies conducted with DNA

Franco

Silva

Castro

et al. 2018

Environmental Pollution

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The present work evaluates the action of nitroreductase enzyme immobilized on Tosylactivated magnetic particles (MP-Tosyl) on three disperse dyes which contain nitro and azo groups. The dyes included Disperse Red 73 (DR 73), Disperse Red 78 (DR 78), and Disperse Red 167 (DR 167). The use of a magnet enabled the rapid and easy removal of the immobilized enzyme after biotransformation; this facilitated the identification of the products generated using high-performance liquid chromatography with diode array detector (HPLC-DAD) and mass spectrometry (LC-MS/MS). The main products formed by the in vitro biotransformation were identified as the product of nitro group reduction to the correspondent amine groups, which were denoted as follows: 50% of 2-(2-(4-((2-cyanoethyl)(ethyl)amino)phenyl)hydrazinyl)-5-nitrobenzonitrile, 98% of 3-((4-((4-amino-2-chlorophenyl) diazenyl)phenyl) (ethyl)amino)propanenitrile and 99% of (3-acetamido-4 - ((4-amino-2-chlorophenyl) diazenyl) phenyl) azanediyl) bis (ethane-2,1-diyl) for DR 73, DR 78 and DR 167, respectively. Based on the docking studies, the dyes investigated were found to be biotransformed by nitroreductase enzyme due to their favorable interaction with the active site of the enzyme. Theoretical results show that DR73 dye exhibits a relatively lower rate of degradation; this is attributed to the cyanide substituent which affects the electron density of the azo group. The docking studies also indicate that all the dyes presented significant reactivity towards DNA. However, Disperse Red 73 was found to exhibit a substantially higher reactivity compared to the other dyes; this implies that the dye possesses a relatively higher mutagenic power. The docking results also show that DR 73, DR 78 and DR 167 may be harmful to both humans and the environment, since the mutagenicity of nitro compounds is associated with the products formed during the reduction of nitro groups. These products can interact with biomolecules, including DNA, causing toxic and mutagenic effects.

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Assessment of molecular binding of Hoechst 33258 analogues into DNA using docking and MM/GBSA approach

Cited by 12 publications

References 65 publications

Identification of biotransformation products of disperse dyes with rat liver microsomes by LC-MS/MS and theoretical studies with DNA: Structure-mutagenicity relationship using Salmonella/microsome assay

Identification of biotransformation products of disperse dyes with rat liver microsomes by LC-MS/MS and theoretical studies with DNA: Structure-mutagenicity relationship using Salmonella/microsome assay

Theoretical Insight into the Library Screening Approach for Binding of Intermolecular G-Quadruplex RNA and Small Molecules through Docking and Molecular Dynamics Simulation Studies

Biotransformation of disperse dyes using nitroreductase immobilized on magnetic particles modified with tosyl group: Identification of products by LC-MS-MS and theoretical studies conducted with DNA

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