Influence of conventional hydrogen bonds in the intercalation of phenanthroline derivatives with DNA: The important role of the sugar and phosphate backbone

Sánchez-González, Ángel; Grenut, Pierre; Gil, Adrià

doi:10.1002/jcc.26836

Cited by 8 publications

(4 citation statements)

References 114 publications

(308 reference statements)

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“…EDA serves as a powerful tool for scrutinizing the intricacies of bonding within both organic and inorganic compounds [60] . The results give the total binding energies (E int ), which equal the summation of three essential contributions, the orbital interaction E orb the electrostatic interaction (E elstat ), the repulsive exchange (Pauli) interaction E Pauli .…”

Section: Resultsmentioning

confidence: 99%

“…Repulsive exchange (Pauli) energy (ΔE Pauli ), orbital (covalent) energy (ΔE orb ), electrostatic energy (ΔE elect ), and dispersion energy (ΔE dis ). [35,36] The energies of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of molecules were calculated. Quantum chemical parameters of molecules reactivity: HOMO-LUMO energy gap, chemical hard-ness (η = (E LUMO À E HOMO )/2), [37] electronic chemical potential (μ = (E HOMO + E LUMO )/2), [29,38] global softness (S = 1/η) and electrophilicity index (ω = μ2/2η) [39,40] parameters were calculated for two molecules.…”

Section: Quantum Theory Of Atoms In Moleculesmentioning

confidence: 99%

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In Vitro and In Silico Studies on Benzimidazole‐Based Compounds

Bouchekioua,

Akkoc,

Menacer

2024

ChemistrySelect

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Colon cancer remains a significant health concern, necessitating the synthesis of novel therapeutic agents. Benzimidazole derivatives have shown promising anticancer potential. In this study, two benzimidazole derivatives were synthesized, and their antiproliferative activities were investigated in vitro against the human colon colorectal cancer cell line and the human normal lung fibroblast cell line. The cell viability revealed that molecule 3 had high antiproliferative activity and inhibited the growth of DLD‐1 cells for 48 h. Furthermore, molecule 3 was found to have more selectivity against the human normal cell line. Computational calculations were performed to predict the molecular properties of molecules using the B3LYP/6‐311++(2d,2p) density functional theory level. The quantum theory of atoms in molecules (QTAIM) and energy decomposition analysis (EDA) were utilized to investigate the nature of the interatomic bonding existing among the studied molecules. The ultraviolet‐visible (UV–vis) results for molecules were calculated using time‐dependent density‐functional theory (TD‐DFT). The chemical reactivity and molecular stability were also investigated by DFT computational analysis. The molecular docking and dynamics simulations were conducted, and their results reveal their concordance with the experimental results. Molecule 3 has better anti‐cancer activity against colon cancer targets (PDB ID: 2HQ6) compared to molecule 2.

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Section: Resultsmentioning

confidence: 99%

Section: Quantum Theory Of Atoms In Moleculesmentioning

confidence: 99%

In Vitro and In Silico Studies on Benzimidazole‐Based Compounds

Bouchekioua,

Akkoc,

Menacer

2024

ChemistrySelect

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“…In general, chemotherapy drugs are categorized as either groove binders or intercalators of DNA, which can result in changes in the parameters of the duplex structure, leading to therapeutic effects. 14 Previous studies have shown that flat molecules interacting from the minor groove side eject the mismatched DNA bases and bind through π-stacking. 15 In the intercalation mode, small molecules are included between the two base pairs of DNA, which are not in direct bonding.…”

Section: Introductionmentioning

confidence: 99%

Unveiling the Intermolecular Interactions between Drug 5-Fluorouracil and Watson–Crick/Hoogsteen Base Pairs: A Computational Analysis

Venkataramanan,

Suvitha,

Sahara

2024

ACS Omega

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The adsorption of 5-fluorouracil (5FU) on Watson–Crick (WC) base pairs and Hoogsteen (HT) base pairs has been studied using the dispersion-corrected density functional theory (DFT). The adsorption, binding energy, and thermochemistry for the drug 5FU on the WC and HT base pairs were determined. The most stable geometries were near planar geometry, and 5FU has a higher preference for WC than HT base pairs. The adsorption energies of 5FU on nucleobase pairs are consistently higher than pristine nucleobase pairs, indicating that nucleobase pair cleavage is less likely during the adsorption of the 5FU drug. The enthalpy change for the formation of 5FU–DNA base pairs is higher than that for the formation of 5FU–nucleobases and is enthalpy-driven. The E gap of AT base pairs is higher, suggesting that their chemical reactivity toward further reaction would be less than that of GC base pairs. The electron density difference (EDD) analysis shows a significant decrease in electron density in aromatic regions on the purine bases (adenine/guanine) compared to the pyrimidine bases. The MESP diagram of the stable 5FU–nucleobase pair complexes shows a directional interaction, with the positive regions in a molecule interacting with the negative region of other molecules. The atoms in molecule analysis show that the ρ(r) values of CO···H–N are higher than those of N···H/N–H···O. The N···H intermolecular bonds between the base pair/drug and nucleobases are weak, closed shell interactions and are electrostatic in nature. The noncovalent interaction analysis shows that several new spikes are engendered along with an increase in their strength, which indicates that the H-bonding interactions are stronger and play a dominant role in stabilizing the complexes. Energy decomposition analysis shows that the drug–nucleobase pair complex has a marginal increase in the electrostatic contributions compared to nucleobase pair complexes.

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“…These earlier studies provide utilitarian information about the interaction of CLQ with DNA; however, the molecular level picture about the DNA-drug binding such as the importance of the chemical nature and arrangement of nucleobases of DNA as well as the particular functional group of CLQ responsible for the interaction is almost lacking. The groove as well as intercalator mode of the binding of different chemical molecules with DNA has been studied earlier and has been correlated with the toxicity effect of molecules on DNA. − It is known that the sequence of DNA controls many important biological processes such as replication and transcription, which can play an important role in the action of CLQ . Hence, it is essential to acquire the molecular level picture related to the role of the nucleobases as well as the functional group responsible for the action of CLQ to enhance the understanding of its action.…”

Section: Introductionmentioning

confidence: 99%

Nucleobase Specific Understanding about the Interaction of Antimalarial Drug Chloroquine with Duplex DNA

et al. 2023

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Antimalarial action of a drug is closely associated with the interaction with the parasite's DNA. Hence, in this study, the interaction of an important antimalarial drug, chloroquine (CLQ), has been investigated with six different sequences of DNA having pure adenine (A)−thymine (T) and pure cytosine (C)−guanine (G) as well as mixed nucleobases to achieve the nucleobase level of information in the binding of antimalarial drug with DNA along with binding induced stabilization/destabilization of DNA using different spectroscopic methods and molecular dynamics simulation technique. Further, the experiments have been also performed with 4-amino-7-chloroquinoline (7CLQ), an analogue of CLQ, to understand the role of the quinoline ring and side chain of CLQ in the binding with different sequences of DNA. The binding efficiency of CLQ with any sequence of DNA is higher than 7CLQ suggesting that the presence of charge on CLQ plays a prominent role in DNA binding. The data suggest that the binding of drug as well as induced stabilization of DNA depends significantly on the nature as well as the arrangement of the nucleobases. In general, the binding of CLQ with pure CG DNA is higher than with pure AT DNA; moreover, it prefers an alternate order of CG/AT than continual nucleobases in duplex DNA. CLQ predominately accommodates in the minor groove of AT DNA and prefers to form hydrogen bond mostly with the adenine nucleobase. In contrast to AT DNA, CLQ intrudes into the both major and minor grooves, but it is primarily accommodated into the major groove of CG DNA. CLQ forms a hydrogen bond mainly with guanine in the major groove and cytosine in the minor groove of CG DNA which enhances the binding of CLQ compared to AT DNA as well as induces higher stabilization in CG DNA. The molecular level information obtained about the functional group responsible for the interaction of CLQ as well as the role of chemical nature of nucleobases along with its ordering on the binding of CLQ with DNA may be useful in comprehensive understanding of its action mechanism.

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Influence of conventional hydrogen bonds in the intercalation of phenanthroline derivatives with DNA: The important role of the sugar and phosphate backbone

Cited by 8 publications

References 114 publications

In Vitro and In Silico Studies on Benzimidazole‐Based Compounds

In Vitro and In Silico Studies on Benzimidazole‐Based Compounds

Unveiling the Intermolecular Interactions between Drug 5-Fluorouracil and Watson–Crick/Hoogsteen Base Pairs: A Computational Analysis

Nucleobase Specific Understanding about the Interaction of Antimalarial Drug Chloroquine with Duplex DNA

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