A novel coumarin-triazole-thiophene hybrid: synthesis, characterization, ADMET prediction, molecular docking and molecular dynamics studies with a series of SARS-CoV-2 proteins

Journal of Chemical Sciences, Год журнала: 2023, Номер 135(1)

Опубликована: Янв. 18, 2023

Язык: Английский

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Molnupiravir: A Versatile Prodrug against SARS-CoV-2 Variants

Metabolites, Год журнала: 2023, Номер 13(2), С. 309 - 309

Опубликована: Фев. 20, 2023

The nucleoside analog β-D-N4-hydroxycytidine is the active metabolite of prodrug molnupiravir and accepted as an efficient drug against COVID-19. Molnupiravir targets RNA-dependent RNA polymerase (RdRp) enzyme, which responsible for replicating viral genome during replication process certain types viruses. It works by disrupting normal function RdRp causing it to make mistakes genome. These can prevent from being transcribed, converted into a complementary DNA template, translated, or functional protein. By these crucial steps in process, effectively inhibit virus reduce its ability cause disease. This review article sheds light on impact SARS-CoV-2 variants concern, such delta, omicron, hybrid/recombinant variants. detailed mechanism molecular interactions using docking dynamics have also been covered. safety tolerability patients with comorbidities emphasized.

Язык: Английский

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A novel cyclobutane-derived thiazole–thiourea hybrid with a potency against COVID-19 and tick-borne encephalitis: synthesis, characterization, and computational analysis

Journal of Sulfur Chemistry, Год журнала: 2023, Номер 45(1), С. 120 - 137

Опубликована: Сен. 22, 2023

AbstractIn the present contribution, a novel cyclobutane-derived thiazole–thiourea hybrid 1-(4-(3-methyl-3-phenylcyclobutyl)thiazol-2-yl)−3-(p-tolyl)thiourea (1), which was readily fabricated from addition of p-isothiocyanatotoluene to 4-(3-methyl-3-phenylcyclobutyl)thiazol-2-amine, is reported. The formation 1 firmly confirmed by means elemental analysis, and IR 1H NMR spectroscopy. Theoretical DFT-based computations were additionally applied reveal structure electronic features title compound. chemical activity estimated reactivity descriptors MEP surface. ADMET properties reported compound predicted in silico using online services. Potential inhibition series SARS-CoV-2 tick-borne encephalitis proteins studied molecular docking, which, turn, allowed ligand efficiency scores for resulting protein–1 complexes. It established that exhibits best against Nonstructural protein 14 (N7-MTase) virus (TBEV) glycoprotein amongst TBE proteins, respectively.KEYWORDS: Cyclobutanethiazolethioureasynthesiscomputational studymolecular docking Disclosure statementNo potential conflict interest author(s).

Язык: Английский

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Synthesis, Characterization and Computational Analysis of Thiophene-2,5-Diylbis((3-Mesityl-3-Methylcyclobutyl)Methanone)

Polycyclic aromatic compounds, Год журнала: 2022, Номер 43(7), С. 6107 - 6125

Опубликована: Авг. 22, 2022

Язык: Английский

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In silico analyses of betulin: DFT studies, corrosion inhibition properties, ADMET prediction, and molecular docking with a series of SARS-CoV-2 and monkeypox proteins

Structural Chemistry, Год журнала: 2022, Номер 34(4), С. 1545 - 1556

Опубликована: Окт. 27, 2022

Язык: Английский

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DFT, ADMET, molecular docking and molecular dynamics studies of pyridoxal

Journal of the Indian Chemical Society, Год журнала: 2023, Номер 100(3), С. 100926 - 100926

Опубликована: Янв. 31, 2023

Язык: Английский

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N'-isonicotinoylpicolinohydrazonamide: Synthesis, crystal structure, DFT and ADMET studies, and in silico inhibition properties toward a series of COVID-19 proteins

Polyhedron, Год журнала: 2023, Номер 235, С. 116362 - 116362

Опубликована: Март 1, 2023

Язык: Английский

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Unraveling DDIT4 in the VDR-mTOR pathway: a novel target for drug discovery in diabetic kidney disease

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Март 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.

Язык: Английский

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Ambroxol: Insight into the Crystal Structure, Hirshfeld Surface Analysis and Computational Study

Polycyclic aromatic compounds, Год журнала: 2022, Номер 43(3), С. 2599 - 2617

Опубликована: Март 14, 2022

We report detailed studies of Form II ambroxol, which crystal packing was examined in detail by a Hirshfeld surface analysis. Molecules the structure are primarily linked through N–H···N and O–H···O hydrogen bonds C–Br···π interactions. The molecular is characterized intermolecular contacts H···X (X = H, C, N, O, Br) C/O/Br···Br. overall topology energy distributions ambroxol also established. mainly dispersion title compound further studied IR UV-vis spectroscopy. Intermolecular dictate clearly revealed discrepancies between experimental calculated spectra region 3000–4000 cm−1. DFT/B3LYP/6-311++G(d,p) calculations were performed to verify as well its electronic optical properties. Molecular docking applied examine influence on series SARS-CoV-2 proteins. molecule interacts much more efficiently with proteins comparison Favipiravir, showing best binding affinity RdRp-RNA nsp14 (N7-MTase).

Язык: Английский

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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

Pharmaceuticals, Год журнала: 2023, Номер 16(2), С. 286 - 286

Опубликована: Фев. 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.

Язык: Английский

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