Antitrypanosomal Potential of Chalcone‐Based Ursolic Acid Derivatives via Ligand‐Based Virtual Screening, DMPK Analyses, Molecular Dynamics Simulation, and MM/GBSA Binding Energy DOI
João Victor Serra Nunes, Matheus Nunes da Rocha, Victor Moreira de Oliveira

и другие.

ChemistrySelect, Год журнала: 2024, Номер 9(44)

Опубликована: Ноя. 1, 2024

Abstract Chagas disease, caused by the protozoan parasite Trypanosoma cruzi and transmitted mainly triatomine insects, represents a significant challenge to public health, especially in impoverished regions. Current treatments, such as benznidazole nifurtimox, have limitations, including serious side effects reduced efficacy chronic phase. This work aims evaluate antitrypanosomal activity of ursolic acid‐derived chalcones (UACD) using ligand‐based virtual screening approach. To this end, series independent molecular docking simulations were carried out (via AutoDock Vina code) with proliferation cycle enzymes TcGAPDH cruzain. The most favorable candidates underwent drug metabolism pharmacokinetics (DMPK) analyses dynamics (MD) estimate pharmacokinetic pharmacodynamic profile. Molecular showed that UACD derivatives better specificity for enzyme, emphasizing acid UACD3 (affinity energy = −9.4 kcal/mol each). DMPK prediction present viable apparent permeability ( P app ) promotes an excellent absorbed fraction (in 10⁻⁶ cm/s). MD derivative free when binding enzyme (−13.27 ± 1.87 kcal/mol) interacting active site residues Cys166 Thr167. However, both ligands appear be alternative therapies treating disease.

Язык: Английский

Integrative bioinformatics analysis reveals CGAS as a ferroptosis-related signature gene in sepsis and screens the potential natural inhibitors of CGAS DOI
Jiaxi Chen,

Mingmei Feng,

Tianyao Zhang

и другие.

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 139778 - 139778

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Allosteric covalent inhibition of TOE1 as potential unexplored anti-cancer target: structure-based virtual screening and covalent molecular dynamics analysis DOI Creative Commons
Ibrahim Oluwatobi Kehinde, Ernest Oduro‐Kwateng,

Mahmoud E. S. Soliman

и другие.

Journal of Receptors and Signal Transduction, Год журнала: 2024, Номер 44(3), С. 97 - 106

Опубликована: Май 3, 2024

Cancer remains a formidable challenge in therapeutic development owing to its complex molecular mechanisms and resistance conventional treatments. Recent evidence suggests that TOE1 may play role cancer progression, making it an attractive target for interventions, nevertheless, very limited research literature has explored the potential of inhibitors as anti-cancer. Herein, by exploring library 13,900 cysteine-targeted covalent via comprehensive virtual screening process, we sought identify compounds could be developed into effective therapies against TOE1. The were first screened based on their binding affinity, followed compliance with drug-like properties, finally, modeling reactive cysteine (Cys80). A total 66 compounds, 28 3 found have higher affinities, optimum drug-likeness, docking scores, respectively, than reference compound. top three 0462, 2204, 7034, demonstrated favorable interaction profiles, dynamics, free energetics, per-residue energy contributions compared Notably, compound 0462 contributed highest significantly enhanced stability rigidity TOE1, while restricting residue flexibility. This study provides account mechanics underpinning inhibition providing compelling case further investigation translation inhibitors, particularly novel therapeutics cancer.

Язык: Английский

Процитировано

2
Antitrypanosomal Potential of Chalcone‐Based Ursolic Acid Derivatives via Ligand‐Based Virtual Screening, DMPK Analyses, Molecular Dynamics Simulation, and MM/GBSA Binding Energy DOI
João Victor Serra Nunes, Matheus Nunes da Rocha, Victor Moreira de Oliveira

и другие.

ChemistrySelect, Год журнала: 2024, Номер 9(44)

Опубликована: Ноя. 1, 2024

Abstract Chagas disease, caused by the protozoan parasite Trypanosoma cruzi and transmitted mainly triatomine insects, represents a significant challenge to public health, especially in impoverished regions. Current treatments, such as benznidazole nifurtimox, have limitations, including serious side effects reduced efficacy chronic phase. This work aims evaluate antitrypanosomal activity of ursolic acid‐derived chalcones (UACD) using ligand‐based virtual screening approach. To this end, series independent molecular docking simulations were carried out (via AutoDock Vina code) with proliferation cycle enzymes TcGAPDH cruzain. The most favorable candidates underwent drug metabolism pharmacokinetics (DMPK) analyses dynamics (MD) estimate pharmacokinetic pharmacodynamic profile. Molecular showed that UACD derivatives better specificity for enzyme, emphasizing acid UACD3 (affinity energy = −9.4 kcal/mol each). DMPK prediction present viable apparent permeability ( P app ) promotes an excellent absorbed fraction (in 10⁻⁶ cm/s). MD derivative free when binding enzyme (−13.27 ± 1.87 kcal/mol) interacting active site residues Cys166 Thr167. However, both ligands appear be alternative therapies treating disease.

Язык: Английский

Процитировано

0