Anticancer drug IUdR and other 5-halogen derivatives of 2′-deoxyuridine: conformers, hydrates, and structure–activity relationships

Palafox, M. Alcolea

doi:10.1007/s11224-013-0225-1

Cited by 10 publications

(6 citation statements)

References 94 publications

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“…From a rigorous theoretical point of view, the latter procedure is the preferred. Moreover, previous studies carried out by us indicated that explicit solvent molecules affect much more on the molecular structure than implicit solvent . Thus, it is the procedure that it is followed in the present work.…”

Section: Resultsmentioning

confidence: 98%

“…In general, DFT methods appear as the most suitable today because they offer a compromise between the important demands put on computer power and time, and the desired chemical accuracy. Furthermore, these methods have been used satisfactorily in many spectroscopic studies, in nucleosides, DNA base pairs, water cluster of nucleobases, biological molecules, and in drug designing, in particular the M062X method selected here …”

Section: Computational Methodologymentioning

confidence: 99%

“…The methodology used here for the hydration, the so‐called Modified Scheme of Monosolvation (MSM) from Pullman, was previously used by us in the hydration of several nucleosides . The hydration effects on the microhelixes with U, s 2 U, s 4 U, and s 2,4 U were determined by different numbers of water molecules in explicit form surrounding the nucleobase up to 20.…”

Section: Computational Methodologymentioning

confidence: 99%

“…Several parameters characterize the conformation of a nucleotide, namely the orientation of the purine/pyrimidine base unit regarding the furanose sugar unit (SU), the conformation of SU, and the orientation of the phosphate unit with reference to SU. Following the Saenger's notation, the atomic description of a nucleotide as well as the main endocyclic and exocyclic torsional angles appears as described in Scheme .…”

Section: Definition Of the Parameters In The Microhelixmentioning

confidence: 99%

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Effect of the sulfur atom on S2 and S4 positions of the uracil ring in different DNA:RNA hybrid microhelixes with three nucleotide base pairs

Palafox

2019

Biopolymers

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The effect of the sulphur atom on the uracil ring was analyzed in different DNA:RNA microhelixes with three nucleotide base‐pairs, including uridine, 2‐thiouridine, 4‐thiouridine, 2,4‐dithiouridine, cytidine, adenosine and guanosine. Distinct backbone and helical parameters were optimized at different density functional (DFT) levels. The Watson‐Crick pair with 2‐thiouridine appears weaker than with uridine, but its interaction with water molecules appears easier. Two types of microhelixes were found, depending on the H‐bond of H2′ hydroxyl atom: A‐type appears with the ribose ring in 3E‐envelope C3′‐endo, and B‐type in 2E‐envelope C2′‐endo. B‐type is less common but it is more stable and with higher dipole‐moment. The sulphur atoms significantly increase the dipole‐moment of the microhelix, as well as the rise and propeller twist parameters. Simulations with four Na atoms H‐bonded to the phosphate groups, and further hydration with explicit water molecules were carried out. A re‐definition of the numerical value calculation of several base‐pair and base‐stacking parameters is suggested.

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Section: Resultsmentioning

confidence: 98%

Section: Computational Methodologymentioning

confidence: 99%

Section: Computational Methodologymentioning

confidence: 99%

Section: Definition Of the Parameters In The Microhelixmentioning

confidence: 99%

See 2 more Smart Citations

Effect of the sulfur atom on S2 and S4 positions of the uracil ring in different DNA:RNA hybrid microhelixes with three nucleotide base pairs

Palafox

2019

Biopolymers

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“…The Modified Scheme of Monosolvation (MSM) [40] was used for the hydration of all the thio-nucleobases up to 30 water molecules, which includes the first and second hydration shells. This methodology has been utilized most successfully by us earlier in the simulation of the first hydration shell of 2TU [13], and in several nucleobases [41,42] and nucleosides [43,44].…”

Section: Computational Methodologymentioning

confidence: 99%

Biomolecules of 2-Thiouracil, 4-Thiouracil and 2,4-Dithiouracil: A DFT Study of the Hydration, Molecular Docking and Effect in DNA:RNAMicrohelixes

Palafox

Benial²,

Rastogi³

2019

IJMS

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The molecular structure of 2-thiouracil, 4-thiouracil and 2,4-dithiouracil was analyzed under the effect of the first and second hydration shell by using the B3LYP density functional (DFT) method, and the results were compared to those obtained for the uracil molecule. A slight difference in the water distribution appears in these molecules. On the hydration of these molecules several trends in bond lengths and atomic charges were established. The ring in uracil molecule appears easier to be deformed and adapted to different environments as compared to that when it is thio-substituted. Molecular docking calculations of 2-thiouracil against three different pathogens: Bacillus subtilis, Escherichia coli and Candida albicans were carried out. Docking calculations of 2,4-dithiouracil ligand with various targeted proteins were also performed. Different DNA: RNA hybrid microhelixes with uridine, 2-thiouridine, 4-thiouridine and 2,4-dithiouridine nucleosides were optimized in a simple model with three nucleotide base pairs. Two main types of microhelixes were analyzed in detail depending on the intramolecular H-bond of the 2′-OH group. The weaker Watson–Crick (WC) base pair formed with thio-substituted uracil than with unsubstituted ones slightly deforms the helical and backbone parameters, especially with 2,4-dithiouridine. However, the thio-substitution significantly increases the dipole moment of the A-type microhelixes, as well as the rise and propeller twist parameters.

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Interplay of thermochemistry and structural chemistry, the journal (volume 25, 2014, issues 1–2) and the discipline

2015

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Anticancer drug IUdR and other 5-halogen derivatives of 2′-deoxyuridine: conformers, hydrates, and structure–activity relationships

Cited by 10 publications

References 94 publications

Effect of the sulfur atom on S2 and S4 positions of the uracil ring in different DNA:RNA hybrid microhelixes with three nucleotide base pairs

Effect of the sulfur atom on S2 and S4 positions of the uracil ring in different DNA:RNA hybrid microhelixes with three nucleotide base pairs

Biomolecules of 2-Thiouracil, 4-Thiouracil and 2,4-Dithiouracil: A DFT Study of the Hydration, Molecular Docking and Effect in DNA:RNAMicrohelixes

Interplay of thermochemistry and structural chemistry, the journal (volume 25, 2014, issues 1–2) and the discipline

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