1-hydroxy-6,6-Dimethyl-3-Phenyl-1,6-Dihydropyridine-2,5-Dione as a Promising Inhibitor of the SARS-CoV-2 Proteins: insight into the Crystal Structure, Hirshfeld Surface Analysis and Computational Study

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1-hydroxy-6,6-Dimethyl-3-Phenyl-1,6-Dihydropyridine-2,5-Dione as a Promising Inhibitor of the SARS-CoV-2 Proteins: insight into the Crystal Structure, Hirshfeld Surface Analysis and Computational Study. / Babashkina, Maria G.; Taskin-Tok, Tugba; Burkhanova, Tatyana et al.
In: Polycyclic Aromatic Compounds, Vol. 43, No. 5, 28.05.2023, p. 4729-4749.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{6ac861403d2643afbc128431d84c172c,

title = "1-hydroxy-6,6-Dimethyl-3-Phenyl-1,6-Dihydropyridine-2,5-Dione as a Promising Inhibitor of the SARS-CoV-2 Proteins: insight into the Crystal Structure, Hirshfeld Surface Analysis and Computational Study",

abstract = "In this work detailed studies of 1-hydroxy-6,6-dimethyl-3-phenyl-1,6-dihydropyridine-2,5-dione (1), which is of potential biological interest, are reported. The molecule of 1 is stabilized by O–H···O and two C–H···O hydrogen bonds. The former interaction yields a pseudo-aromatic hydrogen bonded five-membered ring. The overall crystal packing of 1 is mainly described by O–H···O hydrogen bonds and π···π interactions, yielding a 1D supramolecular ribbon-like chain. These chains are linked through weak C–H···O hydrogen bonds. The reciprocal favored intermolecular H···H/C/O and C···C contacts are main contributors to the total Hirshfeld surface of 1. The structure, electronic and optical properties of 1 were verified with the DFT calculations, which revealed that 1 is a strong electrophile with the most pronounced nucleophilic and electrophilic centers located on the carbonyl oxygen atoms and on the hydroxyl hydrogen atom, respectively. Values for the calculated polarizability and first-order hyperpolarizability parameters for a molecule of 1 are higher in comparison to those of urea. Bioavailability, druggability as well as absorption, distribution, metabolism, excretion and toxicity properties of 1 were evaluated using the SwissADME, BOILED-Egg and ProTox-II tools. It was established that for 1, the human blood-brain barrier penetration property is positive and gastrointestinal absorption property is high with the negative PGP effect on the molecule. Molecular docking was applied to examine the influence of this compound on a series of the SARS-CoV-2 proteins, of which 1 exhibits the best affinity behavior toward RdRp-RNA, nonstructural protein 14 (N7-MTase) and N protein (NCB site).",

author = "Babashkina, {Maria G.} and Tugba Taskin-Tok and Tatyana Burkhanova and Safin, {Damir a.}",

note = "The authors thank Esin Akı Yalcin and the research group for technical assistance. This work was supported by state assignment of the Ministry of Science and Higher Education of the Russian Federation (Project Reg. No. 720000Ф.99.1.БЗ85АА13000).",

year = "2023",

month = may,

day = "28",

doi = "10.1080/10406638.2022.2094420",

language = "English",

volume = "43",

pages = "4729--4749",

journal = "Polycyclic Aromatic Compounds",

issn = "1040-6638",

publisher = "Taylor and Francis Ltd.",

number = "5",

}

RIS

TY - JOUR

T1 - 1-hydroxy-6,6-Dimethyl-3-Phenyl-1,6-Dihydropyridine-2,5-Dione as a Promising Inhibitor of the SARS-CoV-2 Proteins: insight into the Crystal Structure, Hirshfeld Surface Analysis and Computational Study

AU - Babashkina, Maria G.

AU - Taskin-Tok, Tugba

AU - Burkhanova, Tatyana

AU - Safin, Damir a.

N1 - The authors thank Esin Akı Yalcin and the research group for technical assistance. This work was supported by state assignment of the Ministry of Science and Higher Education of the Russian Federation (Project Reg. No. 720000Ф.99.1.БЗ85АА13000).

PY - 2023/5/28

Y1 - 2023/5/28

N2 - In this work detailed studies of 1-hydroxy-6,6-dimethyl-3-phenyl-1,6-dihydropyridine-2,5-dione (1), which is of potential biological interest, are reported. The molecule of 1 is stabilized by O–H···O and two C–H···O hydrogen bonds. The former interaction yields a pseudo-aromatic hydrogen bonded five-membered ring. The overall crystal packing of 1 is mainly described by O–H···O hydrogen bonds and π···π interactions, yielding a 1D supramolecular ribbon-like chain. These chains are linked through weak C–H···O hydrogen bonds. The reciprocal favored intermolecular H···H/C/O and C···C contacts are main contributors to the total Hirshfeld surface of 1. The structure, electronic and optical properties of 1 were verified with the DFT calculations, which revealed that 1 is a strong electrophile with the most pronounced nucleophilic and electrophilic centers located on the carbonyl oxygen atoms and on the hydroxyl hydrogen atom, respectively. Values for the calculated polarizability and first-order hyperpolarizability parameters for a molecule of 1 are higher in comparison to those of urea. Bioavailability, druggability as well as absorption, distribution, metabolism, excretion and toxicity properties of 1 were evaluated using the SwissADME, BOILED-Egg and ProTox-II tools. It was established that for 1, the human blood-brain barrier penetration property is positive and gastrointestinal absorption property is high with the negative PGP effect on the molecule. Molecular docking was applied to examine the influence of this compound on a series of the SARS-CoV-2 proteins, of which 1 exhibits the best affinity behavior toward RdRp-RNA, nonstructural protein 14 (N7-MTase) and N protein (NCB site).

AB - In this work detailed studies of 1-hydroxy-6,6-dimethyl-3-phenyl-1,6-dihydropyridine-2,5-dione (1), which is of potential biological interest, are reported. The molecule of 1 is stabilized by O–H···O and two C–H···O hydrogen bonds. The former interaction yields a pseudo-aromatic hydrogen bonded five-membered ring. The overall crystal packing of 1 is mainly described by O–H···O hydrogen bonds and π···π interactions, yielding a 1D supramolecular ribbon-like chain. These chains are linked through weak C–H···O hydrogen bonds. The reciprocal favored intermolecular H···H/C/O and C···C contacts are main contributors to the total Hirshfeld surface of 1. The structure, electronic and optical properties of 1 were verified with the DFT calculations, which revealed that 1 is a strong electrophile with the most pronounced nucleophilic and electrophilic centers located on the carbonyl oxygen atoms and on the hydroxyl hydrogen atom, respectively. Values for the calculated polarizability and first-order hyperpolarizability parameters for a molecule of 1 are higher in comparison to those of urea. Bioavailability, druggability as well as absorption, distribution, metabolism, excretion and toxicity properties of 1 were evaluated using the SwissADME, BOILED-Egg and ProTox-II tools. It was established that for 1, the human blood-brain barrier penetration property is positive and gastrointestinal absorption property is high with the negative PGP effect on the molecule. Molecular docking was applied to examine the influence of this compound on a series of the SARS-CoV-2 proteins, of which 1 exhibits the best affinity behavior toward RdRp-RNA, nonstructural protein 14 (N7-MTase) and N protein (NCB site).

UR - http://www.scopus.com/inward/record.url?partnerID=8YFLogxK&scp=85133436849

UR - https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=tsmetrics&SrcApp=tsm_test&DestApp=WOS_CPL&DestLinkType=FullRecord&KeyUT=000821011800001

U2 - 10.1080/10406638.2022.2094420

DO - 10.1080/10406638.2022.2094420

M3 - Article

VL - 43

SP - 4729

EP - 4749

JO - Polycyclic Aromatic Compounds

JF - Polycyclic Aromatic Compounds

SN - 1040-6638

IS - 5

ER -

ID: 41589038