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

Identification of Novel HPK1 Hit Inhibitors: From In Silico Design to In Vitro Validation DOI Open Access
Israa H. Isawi,

Rayan M. Obeidat,

Soraya Alnabulsi

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(9), С. 4366 - 4366

Опубликована: Май 4, 2025

Hematopoietic progenitor kinase 1 (HPK1), a negative regulator of T-cells, B-cells, and dendritic cells, has gained attention in antitumor immunotherapy research over the past decade. No HPK1 inhibitor yet reached clinical approval, largely due to selectivity drug-like limitations. Leveraging available structural insights into HPK1, we conducted rational hit identification using structure-based virtual screening 600,000 molecules from ASINEX OTAVA databases. A series molecular docking studies, vitro assays, dynamics simulations were identify viable hits. This approach resulted two promising novel scaffolds, 4H-Pyrido[1,2-a] thieno[2,3-d] pyrimidin-4-one (ISR-05) quinolin-2(1H)-one (ISR-03), neither which previously been reported as an inhibitor. ISR-05 ISR-03 exhibited IC50 values 24.2 ± 5.07 43.9 0.134 µM, respectively, inhibition assays. These hits constitute tractable starting points for future hit-to-lead optimization aimed at developing more effective inhibitors cancer therapy.

Язык: Английский

Процитировано

0

Discovery of novel GluN1/GluN3A NMDA receptor inhibitors using a deep learning-based method DOI
Shihang Wang, Yue Zeng, Hao Yang

и другие.

Acta Pharmacologica Sinica, Год журнала: 2025, Номер unknown

Опубликована: Май 12, 2025

Язык: Английский

Процитировано

0

Exploiting subtractive genomics to identify novel drug targets and new immunogenic candidates against Bordetella pertussis: an in silico study DOI Creative Commons

Mahshid Khazani Asforooshani,

Narjes Noori Goodarzi, Behzad Shahbazi

и другие.

Frontiers in Bioinformatics, Год журнала: 2025, Номер 5

Опубликована: Май 13, 2025

Bordetella pertussis, the causative agent of whooping cough, remains a significant global health concern despite widespread availability vaccines. The persistent reemergence pertussis is driven by bacterium's ongoing genomic evolution, shifting epidemiological patterns, and limitations in current vaccine strategies. These challenges highlight urgent need to identify novel drug targets immunogenic candidates enhance therapeutic preventive measures against B. pertussis. Identification detection factors as potential were performed. Cytoplasmic proteins evaluated for their similarity human proteome, metabolic pathways, gut microbiota. On other hand, surface-exposed using reverse vaccinology approach. A multi-epitope (MEV) was designed based on linear B-cell epitopes three autotransporters beta domain SphB2 scaffold MEV. Molecular docking, immune simulation results, molecular dynamics simulations performed evaluate binding affinity feasibility interaction between chimeric MEVs receptors. Six identified excellent targets, including elongation factor P (WP_003810194.1), Aspartate kinase (WP_010930633.1), 50S ribosomal protein L21 (WP_003807462.1), Homoserine dehydrogenase (WP_003813074.1), Carboxynorspermidine decarboxylase (WP_003814461.1), PTS sugar transporter subunit IIA (WP_010929966.1). nine proteins, BapA (WP_010930805.1), BrkA (WP_010931506.1), (WP_041166323.1), TcfA (WP_010930243.1), FliK (WP_041166144.1), Fimbrial (WP_010930199.1), TolA (WP_010931418.1), DD-metalloendopeptidase (WP_003811022.1), an I78 family peptidase inhibitor (WP_003812179.1). SphB2-based MEV six extracellular loops autotransporters. TLR2, TLR4, HLA-DR-B computationally confirmed dynamics. It appears that involved translation metabolism can be considered targets. Furthermore, this study highlights autotransporter promising There no doubt experimental work should conducted confirm results future.

Язык: Английский

Процитировано

0

On the application of artificial intelligence in virtual screening DOI
Thanawat Thaingtamtanha, R Ravichandran, Francesco Gentile

и другие.

Expert Opinion on Drug Discovery, Год журнала: 2025, Номер unknown

Опубликована: Май 19, 2025

Artificial intelligence (AI) has emerged as a transformative tool in drug discovery, particularly virtual screening (VS), which is crucial initial step identifying potential candidates. This article highlights the significance of AI revolutionizing both ligand-based (LBVS) and structure-based (SBVS) approaches, streamlining enhancing discovery process. The authors provide an overview applications with focus on LBVS SBVS approaches utilized prospective cases where new bioactive molecules were identified experimentally validated. Discussion includes use quantitative structure-activity relationship (QSAR) modeling for LBVS, well its role techniques such molecular docking dynamics simulations. based literature searches all studies published up to March 2025. rapidly transforming VS by leveraging increasing amounts experimental data expanding scalability. These innovations promise enhance efficiency precision across yet challenges curation, rigorous validation models, efficient integration methods remain critical realizing AI's full discovery.

Язык: Английский

Процитировано

0

Piezoelectric Molecular Selection Pump Based on Stokes’ Principle DOI
Yiheng Liu, Nan Sun, Dongchen Tan

и другие.

ACS Applied Engineering Materials, Год журнала: 2025, Номер unknown

Опубликована: Май 25, 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