Quantum-Chemical and Experimental Estimation of Non-Bonding Level (Fermi Level) and π-Electron Afinity of Conjugated Systems

Obernikhina, Nataliya; Pavlenko, O. L.; Kachkovsky, O.D.; Броварец, В. С.

doi:10.1080/10406638.2019.1710855

Cited by 12 publications

(13 citation statements)

References 30 publications

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Section: Resultsmentioning

confidence: 99%

“…DFT calculations were performed by DFT/6-31 (d,p)/wB97XD method using package GAUSSIAN 03. [33] Molecular Docking…”

Section: Methodsmentioning

confidence: 99%

“…Elemental analyses were carried out on a Vario MACRO Cube/Elementar instrument. DFT calculations were performed by DFT/6‐31 (d,p)/wB97XD method using package GAUSSIAN 03 [33] …”

Section: Methodsmentioning

confidence: 99%

“…We may optimistically suppose that the biological activity (or affinity) of conjugated heterocycles is primarily determined by its donor/acceptor properties; their complex with protein fragments can be stabilized by π -π-stack interactions and H-bond formation. Donor -acceptor properties of any conjugated molecule can be estimated quantitatively by changes of the relative positions of their frontier molecular orbitals: highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) by the following index ϕ 0 [32,33] . When ϕ 0 = 0.5, the donor and acceptor properties are mutually balanced; an increase of the parameter (ϕ 0 > 0.5) indicates a predominately donor nature; if ϕ 0 < 0.5, the frontier molecular orbitals are shifted downward, indicating a predominantly acceptor character.…”

Section: Molecular Dockingmentioning

confidence: 99%

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Synthesis, in silico and in vitro Evaluation of Novel Oxazolopyrimidines as Promising Anticancer Agents

Velihina

Scattolin

Bondar

et al. 2020

Helvetica Chimica Acta

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Dedicated to Prof. Antonio Togni on the occasion of his 65th birthday and retirement New potential bioactive oxazolopyrimidines have been synthesized using two main approaches: the pyrimidine ring annulation on a functionalized oxazole and the benzoyl bromide trimerization followed by rearrangement and formation of the oxazolo[5,4-d]pyrimidine scaffold. The docking analyzes have shown that 7piperazine substituted oxazolo[4,5-d]pyrimidines 8a-8c could be potential VEGFR2 inhibitors with high free energy of ligand-protein complex formation (ΔG: À 10.1, À 9.6, À 9.8 kcal/mol, respectively). In vitro antitumor assays confirmed theoretical predictions that oxazolo[4,5-d]pyrimidines 8a-8c containing positively charged piperazine moiety should demonstrate significantly higher cytotoxic effects. 4-[5-(4-Chlorophenyl)-2-phenyl[1,3] oxazolo[4,5-d]pyrimidin-7-yl]piperazin-1-ium trifluoroacetate (8c) exhibited a slightly higher antiproliferative effect (IC 50 = 0.21 μM) than doxorubicin (IC 50 = 0.36 μM) on MDA-MB-231 cell line and has relatively good results on OVCAR-3 (IC 50 = 1.7 μM) and HCT-116 (IC 50 = 0.24 μM) cells.

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Section: Resultsmentioning

confidence: 99%

“…DFT calculations were performed by DFT/6-31 (d,p)/wB97XD method using package GAUSSIAN 03. [33] Molecular Docking…”

Section: Methodsmentioning

confidence: 99%

“…Elemental analyses were carried out on a Vario MACRO Cube/Elementar instrument. DFT calculations were performed by DFT/6‐31 (d,p)/wB97XD method using package GAUSSIAN 03 [33] …”

Section: Methodsmentioning

confidence: 99%

Section: Molecular Dockingmentioning

confidence: 99%

See 2 more Smart Citations

Synthesis, in silico and in vitro Evaluation of Novel Oxazolopyrimidines as Promising Anticancer Agents

Velihina

Scattolin

Bondar

et al. 2020

Helvetica Chimica Acta

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“…Where LUMO is an energy of the lowest unoccupied MO, HOMO is an energy of the highest occupied MO, F () is an energy of non-bonding MO ( = -3.561 eV) [21].…”

Section: Positions Of the Frontier Orbitals Of Compounds 1-4 And Its Donor/acceptor Propertiesmentioning

confidence: 99%

In silico binding affinity studies of phenyl-substituted 1,3-oxazoles with protein molecules

et al. 2020

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The new model approach of interaction between the pharmacophores with bio-molecules, fragment-to-fragment, is presented. It is a new step of the molecular modeling and takes correctly into consideration not only the spatial complementarity of the interacted molecules but also the contribution of the stacking π-π-electron interaction and hydrogen bonds. As an example, the correct analysis of the interaction of the biological active phenyl-substituted 1,3-oxazoles with protein fragments is performed. It was shown that the length and energy of the hydrogen bond uniquely depend on the chemical constitution of both components in the created complex [Pharmacophore(Oxazole)-Biomolecule (H-X)]. The binding energy regularly decreases in the series X → O, S, NH (fragments of the corresponding biomolecules). It should be pointed out that introduction of the conjugated phenyl groups at positions 2 and 5 of oxazoles increase the stability of the possibly generated complex Pharmacophore-Biomolecule [Pharm-BioM] with fragments of the corresponding biomolecules along the core of oxazole by 0.2 and 0.5 kcal/mole. At the same time, modeling of the possibly generated complex [Pharm-BioM] by phenyl substituents at position 2 and 5 of 1,3-oxazole with phenylalanine as a fragment of protein molecules additionally stabilizes complex by 2.5 kcal/mole by π-stacking mechanism. It seems, the observed biological activity of the phenyl substituted 1,3-oxazole is rather connected with the possibility to generate the stable complex due to the formation of additional bonds with other fragments (conjugated phenyl core). The calculations give that such substituents do not cause spatial hindrances with the polypeptide chain.

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A Comparative In Vitro Anticancer Evaluation and In Silico Study of New 1‐(1,3‐Oxazol‐5‐yl)piperidine‐4‐sulfonylamides

Severin,

Obernikhina,

Pilyo

et al. 2024

ChemistrySelect

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In this work, we synthesized a series of new 1,3‐oxazole derivatives comprising the sulfonylamide group and tested their activity against the human tumor cell line panel. This study further explores the stereoelectronic characteristics of 1,3‐oxazol‐5‐sulfonylamides and new 1‐(1,3‐oxazol‐5‐yl)piperidine‐4‐sulfonylamides to connect their anticancer activity to the molecular structure. Combining in vitro and in silico methods, we analyzed how the proximity of the sulfonylamide group to the heterocyclic ring affects the structure–activity interplay. Herein, our assessment is based on the purported complexation of 1,3‐oxazoles with targeted biomolecular fragments involving the π‐stacking interaction and hydrogen bonding within the prospective complexes. Defining the probability of the prospective drug–target interactions, we detail conformational properties, donor/acceptor capabilities, electronic characteristics, and thermodynamic preference of produced sulfanylamide group containing 1,3‐oxazoles toward biomolecular fragments, identifying the nature of variations in anticancer activity.

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Quantum-Chemical and Experimental Estimation of Non-Bonding Level (Fermi Level) and π-Electron Afinity of Conjugated Systems

Cited by 12 publications

References 30 publications

Synthesis, in silico and in vitro Evaluation of Novel Oxazolopyrimidines as Promising Anticancer Agents

Synthesis, in silico and in vitro Evaluation of Novel Oxazolopyrimidines as Promising Anticancer Agents

In silico binding affinity studies of phenyl-substituted 1,3-oxazoles with protein molecules

A Comparative In Vitro Anticancer Evaluation and In Silico Study of New 1‐(1,3‐Oxazol‐5‐yl)piperidine‐4‐sulfonylamides

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