Discovery and Characterization of Two Selective Inhibitors for a Mu-Class Glutathione S-Transferase of 25 kDa from Taenia solium Using Computational and Bioinformatics Tools DOI Creative Commons

César Sánchez-Juárez,

Roberto Flores‐López,

Leonor Sánchez‐Pérez

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 15(1), P. 7 - 7

Published: Dec. 25, 2024

Glutathione S-transferases (GSTs) are promising pharmacological targets for developing antiparasitic agents against helminths, as they play a key role in detoxifying cytotoxic xenobiotics and managing oxidative stress. Inhibiting GST activity can compromise parasite viability. This study reports the successful identification of two selective inhibitors mu-class glutathione S-transferase 25 kDa (Ts25GST) from Taenia solium, named i11 i15, using computationally guided approach. The workflow involved modeling refining 3D structure sequence AlphaFold algorithm all-atom molecular dynamics simulations with an explicit solvent. Representative structures these putative binding site low conservation relative to human GSTs, identified via SILCS methodology, were employed virtual screening through ensemble docking commercial compound library. compounds found reduce enzyme's by 50-70% under assay conditions, while showing reduction only 30-35% GSTM1, demonstrating selectivity Ts25GST. Notable, displayed competitive inhibition CDNB, i15 exhibited non-competitive type.

Language: Английский

Calycosin Inhibit PANoptosis and Alleviate Brain Damage: A Bioinformatics and Experimental Verification Approach DOI

Huiyan An,

Chongyu Shao, Yu He

et al.

ACS Chemical Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 29, 2025

PANoptosis is a newly identified form of cell death that encompasses pyroptosis, apoptosis, and necroptosis. Numerous studies have highlighted the significance in brain ischemia-reperfusion (I/R) injury. Calycosin, natural product with diverse biological activities, has demonstrated significant reduction neuronal caused by ischemic injury modulating multiple pathways. In order to investigate potential mechanisms underlying neuroprotective role calycosin alleviating PANoptosis-induced damage stroke therapy, we used mouse hippocampal line HT22 stimulate ischemia vitro through Oxygen Glucose Deprivation/Reperfusion (OGD/R) established molecular docking assess binding affinity Calycosin key targets dynamics simulations (MDS) study stability ligand-protein complex. The results demonstrate could improve growth HT22, leading enhanced viability, reduced lactate dehydrogenase leakage, decreased apoptosis after OGD/R. It also regulated expression PANoptosis-related genes such as NLRP3, GSDMD, MLKL, RIPK1 increased Bcl-2/Bax ratio, effectively reducing cellular providing protection. Molecular MDS strong activity between targets. Furthermore, successfully passed drug similarity (DS) evaluation exhibited favorable absorption, distribution, metabolism, excretion, toxicity (ADMET) properties activity. conclusion, alleviate inhibiting PANoptosis, inflammation improving Thus, it serve therapy for stroke.

Language: Английский

Citations

0
Identification of novel inhibitors targeting Mycobacterium abscessus InhA through virtual screening, docking, and molecular dynamic simulations DOI Creative Commons

M Hasnain Abbas,

Abdullah R. Alanzi, Kashif Iqbal Sahibzada

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 14, 2025

Language: Английский

Citations

0
Structure-guided virtual screening reveals phytoconstituents as potent cathepsin B inhibitors: Implications for cancer, traumatic brain injury, and Alzheimer’s disease DOI Creative Commons
Nageeb Hassan, Mohammad Furkan, Mohd Shahnawaz Khan

et al.

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 12

Published: April 16, 2025

Cathepsin B (CathB) is a lysosomal cysteine protease involved in various pathological and physiological processes becoming an attractive target for drug intervention complex diseases like cancer, traumatic brain injury (TBI) Alzheimer's disease (AD). The aberrant expression of CathB drives tumor invasiveness metastasis exacerbates neurodegeneration behavioral deficits AD TBI. However, current inhibitors lack clinical translation due to poor selectivity, bioavailability, or toxicity, necessitating novel therapeutic candidates. To address this gap, silico screening was conducted through the structure-guided virtual with IMPPAT 2 phytochemical library potential inhibitors. Using control inhibitor CA-074Me as benchmark, two phytoconstituents, Nicandrenone Picrasidine M, emerged superior binding affinities, ligand efficiency, robust interactions active site residues CathB. These molecules were further validated molecular dynamics (MD) simulations, which supported their ability bind stably pocket thus likely hold durable inhibitory activity. Remarkably, these phytoconstituents exhibited favorable pharmacokinetic ADMET profiles, validate lead compounds. study showed that bioactive compounds could be developed new inhibitors, opening frontier use management such TBI, AD.

Language: Английский

Citations

0
Investigating the potential compounds of Kalanchoe pinnata plant for the treatment of Inflammation utilizing molecular docking and molecular dynamic simulation approach DOI Creative Commons

S. M. Istiaque Hamim,

Miah Roney, Md. Nazim Uddin

et al.

Published: April 1, 2025

Language: Английский

Citations

0
Discovery and Characterization of Two Selective Inhibitors for a Mu-Class Glutathione S-Transferase of 25 kDa from Taenia solium Using Computational and Bioinformatics Tools DOI Creative Commons

César Sánchez-Juárez,

Roberto Flores‐López,

Leonor Sánchez‐Pérez

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 15(1), P. 7 - 7

Published: Dec. 25, 2024

Glutathione S-transferases (GSTs) are promising pharmacological targets for developing antiparasitic agents against helminths, as they play a key role in detoxifying cytotoxic xenobiotics and managing oxidative stress. Inhibiting GST activity can compromise parasite viability. This study reports the successful identification of two selective inhibitors mu-class glutathione S-transferase 25 kDa (Ts25GST) from Taenia solium, named i11 i15, using computationally guided approach. The workflow involved modeling refining 3D structure sequence AlphaFold algorithm all-atom molecular dynamics simulations with an explicit solvent. Representative structures these putative binding site low conservation relative to human GSTs, identified via SILCS methodology, were employed virtual screening through ensemble docking commercial compound library. compounds found reduce enzyme's by 50-70% under assay conditions, while showing reduction only 30-35% GSTM1, demonstrating selectivity Ts25GST. Notable, displayed competitive inhibition CDNB, i15 exhibited non-competitive type.

Language: Английский

Citations

0