Preferability of Molnupiravir, an Anti-COVID-19 Drug, toward Purine Nucleosides: A Quantum Mechanical Study DOI Creative Commons
Mahmoud A. A. Ibrahim, Mohammed N. I. Shehata, Nayra A. M. Moussa

et al.

ACS Omega, Journal Year: 2023, Volume and Issue: 8(30), P. 27553 - 27565

Published: July 18, 2023

Structural aspects of molnupiravir complexed with the RNA SARS-CoV-2 virus have been recently resolved inside RNA-dependent polymerase (RdRp), demonstrating interactions purine nucleosides. However, preference to interact one nucleoside over another has not clearly investigated. Herein, complexation in its active form guanosine and adenosine was compared, using sundry density functional theory calculations. The plausible tautomeric structures drug complex guanosine/adenosine were minutely scrutinized. relative energy findings outlined favorability amino-molnupiravir···keto-amino-guanosine imino-molnupiravir···amino-adenosine optimized complexes. According interaction (Eint) binding (Ebind) values, higher preferential base-pairing recognized Eint/Ebind values -31.16/-21.81 -13.93/-12.83 kcal/mol, respectively. This could be interpreted by presence three two hydrogen bonds within former latter complexes, Observable changes electronic properties global indices reactivity studied complexes also confirmed from quantum atoms molecules noncovalent index support partially covalent nature investigated interactions. For both thermodynamic parameters spontaneous, exothermic, nonrandom states inspected Inspecting solvent effect on more observable amelioration water medium compared gas one. These results would a durable ground for forthcoming studies concerned

Language: Английский

Copper(II) Chelates of Schiff Bases Enriched with Aliphatic Fragments: Synthesis, Crystal Structure, In Silico Studies of ADMET Properties and a Potency against a Series of SARS-CoV-2 Proteins DOI Creative Commons
Elizaveta V. Panova, Julia К. Voronina, Damir A. Safin

et al.

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(2), P. 286 - 286

Published: Feb. 14, 2023

We report two complexes [Cu(LI)2] (1) and [Cu(LII)2] (2) (HLI = N-cyclohexyl-3-methoxysalicylideneimine, HLII N-cyclohexyl-3-ethoxysalicylideneimine). The ligands in both are trans-1,5-N,O-coordinated, yielding a square planar CuN2O2 coordination core. molecule of 1 is with cyclohexyl groups oriented to the opposite sites part molecule, while 2 significantly bent same convex site molecule. It was established that MeOH absorb UV region due intraligand transitions LMCT. Furthermore, UV-vis spectra revealed low intense shoulders visible at about 460 520 nm, which were attributed d–d transitions. Both predicted belong fourth class toxicity negative BBB property positive gastrointestinal absorption property. According molecular docking analysis results, active against all applied SARS-CoV-2 proteins best binding affinity Nsp 14 (N7-MTase), PLpro Mpro. obtained scores either comparable or even higher than those initial ligands. Complex found be more efficient upon interaction comparison complex 2. Ligand efficiency for ligands, also revealed.

Language: Английский

Citations

15
Computational studies of closely related 2-cyanopyrimidine, pyrimidine-2-carboximidamide and 2,4,6-tris(2-pyrimidyl)-1,3,5-triazine with a potency against SARS-CoV-2 DOI
Tuğba Taşkın‐Tok, Damir A. Safin

Monatshefte für Chemie - Chemical Monthly, Journal Year: 2023, Volume and Issue: 155(1), P. 57 - 71

Published: Nov. 1, 2023

Language: Английский

Citations

14
Unraveling DDIT4 in the VDR-mTOR pathway: a novel target for drug discovery in diabetic kidney disease DOI Creative Commons
Haitao Lu, Yuanyuan Jiao, Tianyu Yu

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: March 19, 2024

Introduction: Diabetic kidney disease (DKD) necessitates innovative therapeutic strategies. This study delves into the role of DNA damage-inducing transcription factor 4 (DDIT4) within VDR-mTOR pathway, aiming to identify a novel target for DKD drug discovery. Methods: Transcriptome data from Gene Expression Omnibus Database were analyzed assess expression mTOR and VDR in human renal tissues. Clinical samples patients minimal change (MCD) controls examined, animal model using 20-week-old db/db mice was established. DDIT4 plasmid transfection employed modulate with its components evaluated immunohistochemistry, real-time quantitative PCR (qRT-PCR), Western blotting, enzyme-linked immunosorbent assay (ELISA). Results: Changes pathway observed both model. Overexpression increased decreased levels mTOR, p70s6k, 4E-BP1. Furthermore, treatment regulated autophagy by upregulating LC3I downregulating LC3II expression. Notably, alleviated oxidative stress reducing lipid peroxidation product MDA, while simultaneously increasing superoxide dismutase (SOD) glutathione (GSH), underscoring pathological process potential as target. Conclusion: Unraveling DDIT4’s involvement provides insights discovery, emphasizing future interventions.

Language: Английский

Citations

6
A comparative study of electropolymerization and photopolymerization for the determination of molnupiravir and their application in an electrochemical sensor via computationally designed molecularly imprinted polymers DOI Creative Commons
Ahmet Çetinkaya, Mehmet Altay Ünal, Hasan Nazır

et al.

Microchimica Acta, Journal Year: 2024, Volume and Issue: 191(5)

Published: April 17, 2024

Abstract A comparative analysis of molecularly imprinted polymers based on different synthesis techniques was performed for the recognition molnupiravir (MOL). The polymerizations were with 3-thienyl boronic acid (3-TBA) as a functional monomer by electropolymerization (EP) and guanine methacrylate (GuaM) photopolymerization (PP). Morphological electrochemical characterizations developed sensors investigated to verify constructed sensors. Moreover, quantum chemical calculations used evaluate changes electrode surface at molecular electronic levels. dynamic linear range both designed under optimized experimental conditions found be 7.5 × 10 −12 –2.5 −10 M −13 −11 EP PP, respectively. effect various interfering agents MOL peak current assessed selectivity study. In presence 100 times more agents, RSD recovery values determined. GuaM/MOL@MIP/GCE poly(Py-co-3-PBA)/MOL@MIP/GCE 1.99% 1.72%, Furthermore, MIP-based 98.18–102.69% 98.05–103.72%, addition, relative coefficient ( k ′) proposed sensor evaluated, it exhibited good respect NIP sensor. prepared successfully applied determine in commercial serum samples capsule form. conclusion, provided excellent reproducibility, repeatability, high sensitivity, against molecule. Graphical

Language: Английский

Citations

6
A novel tetrazole–1,8-naphthyridine–amide hybrid: First structurally characterized tetrazolo[1,5-a]-derivative of naphthyridines with a luminescence activity, potency against COVID-19, and anticancer activity DOI
Suman Adhikari,

Sourav Nath,

Tanushree Sen

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1321, P. 139803 - 139803

Published: Aug. 27, 2024

Language: Английский

Citations

6
A Novel Ambroxol-Derived Tetrahydroquinazoline with a Potency against SARS-CoV-2 Proteins DOI Open Access

Alena I. Krysantieva,

Julia К. Voronina, Damir A. Safin

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4660 - 4660

Published: Feb. 28, 2023

We report synthesis of a novel 1,2,3,4-tetrahydroquinazoline derivative, named 2-(6,8-dibromo-3-(4-hydroxycyclohexyl)-1,2,3,4-tetrahydroquinazolin-2-yl)phenol (1), which was obtained from the hydrochloride 4-((2-amino-3,5-dibromobenzyl)amino)cyclohexan-1-ol (ambroxol hydrochloride) and salicylaldehyde in EtOH. The resulting compound produced form colorless crystals composition 1∙0.5EtOH. formation single product confirmed by IR 1H spectroscopy, single-crystal powder X-ray diffraction, elemental analysis. molecule 1 contains chiral tertiary carbon 1,2,3,4-tetrahydropyrimidine fragment crystal structure 1∙0.5EtOH is racemate. Optical properties were revealed UV-vis spectroscopy MeOH it established that absorbs exclusively UV region up to about 350 nm. exhibits dual emission spectra bands at 340 446 nm upon excitation 300 360 nm, respectively. DFT calculations performed verify as well electronic optical 1. ADMET R-isomer evaluated using SwissADME, BOILED-Egg, ProTox-II tools. As evidenced blue dot position BOILED-Egg plot, both human blood-brain barrier penetration gastrointestinal absorption are positive with PGP effect on molecule. Molecular docking applied examine influence structures S-isomer series SARS-CoV-2 proteins. According analysis results, isomers found be active against all proteins best binding affinities Papain-like protease (PLpro) nonstructural protein 3 (Nsp3_range 207-379-AMP). Ligand efficiency scores for inside sites also compared initial ligands. dynamics simulations evaluate stability complexes complex highly unstable, while other stable.

Language: Английский

Citations

13
Ligand-dictated planar versus bent nickel(II) chelates of the Schiff bases: Synthesis, crystal structures, optical properties, DFT and molecular docking studies DOI
Elizaveta V. Panova, Julia К. Voronina, Damir A. Safin

et al.

Inorganic Chemistry Communications, Journal Year: 2024, Volume and Issue: 166, P. 112407 - 112407

Published: April 9, 2024

Language: Английский

Citations

4
Methyl- versus ethyl-directed formation of square-planar Cobalt(II) and octahedral Cobalt(III) chelates of the in situ generated schiff bases DOI
Elizaveta V. Panova, Julia К. Voronina, Damir A. Safin

et al.

Polyhedron, Journal Year: 2024, Volume and Issue: 257, P. 117014 - 117014

Published: April 27, 2024

Language: Английский

Citations

4
Interaction of Hydrazonophenylacetaldehyde Oxime with Acetone: Nitrone versus Oxime DOI
Elizaveta V. Panova, Damir A. Safin

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(36)

Published: Sept. 1, 2024

Abstract Detailed experimental and computational studies of the nitrone 3,3‐dimethyl‐6‐phenyl‐2,3‐dihydro‐1,2,4‐triazin‐4‐oxide ( 2 ), which is a cyclized product an open‐chain isomer 2‐phenyl‐2‐(propan‐2‐ylidenehydrazono)acetaldehyde oxime 1 are reported. The isolated compound was characterized by elemental analysis, powder X‐ray diffraction, IR UV‐vis spectroscopy, spectrofluorometry. Electronic properties were elucidated DFT‐based calculations in water, revealed that both compounds pronounced electrophiles. ADMET predicted using SwissADME, includes BOILED‐Egg method, ProTox‐II online tools. Using molecular docking approach, discussed also to actively interact with all studied herein SARS‐CoV‐2 proteins. most activity for established Nonstructural protein 14 (Nsp14_N7‐MTase). Complex Nsp14_N7‐MTase‐ calculated ligand efficiency scores being close Hit.

Language: Английский

Citations

4
Synthesis, characterization and computational studies of a series of the thiazole-thiazolidinone hybrids DOI
Bana Sardar Abdulrahman, Roshna Bahram Nadr, Rebaz Anwar Omer

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: unknown, P. 140806 - 140806

Published: Nov. 1, 2024

Language: Английский

Citations

4