A Multifaceted Computational Approach to Identify PAD4 Inhibitors for the Treatment of Rheumatoid Arthritis (RA) DOI Creative Commons
Mansour S. Alturki, Mohamed S. Gomaa, Nada Tawfeeq

et al.

Metabolites, Journal Year: 2025, Volume and Issue: 15(3), P. 156 - 156

Published: Feb. 25, 2025

Background/Objectives: Neutrophil cells’ lysis forms the extracellular traps (NETs) to counter foreign body during insults body. Peptidyl arginine deiminase (PAD) participates in this process and is then released into fluid with lysed cell components. In some diseases, patients abnormal function of PADs, especially PAD 4, tend form autoantibodies against citrullinated proteins that are result activity on side chains. Those antibodies, which highly distinct RA, distinctly anti-citrullinated protein antibodies (ACPA). This study used an in-silico drug repurposing approach FDA-approved medications identify potential alternative can inhibit address solutions current limitations existing therapies. Methods: We utilized Maestro Schrödinger as a computational tool for preparing docking simulations 4 enzyme crystal structure retrieved from RCSB Protein Data Bank (PDB ID: 4X8G) while docked obtained Zinc 15 database. The was bound GSK 199—an investigational compound—as positive control molecules. Preparation performed by Wizard tool. Binding pocket determination Glide software (Schrödinger Release 2021–3:Schrödinger, LLC., New York, NY, USA, 2021). validation molecular carried out through redocking 199 superimposition. After that, standard induced fit were performed. Results/Conclusions: Among four hits Pemetrexed, Leucovorin, Chlordiazepoxide, Ioversol, showed highest XP scores providing favorable binding interactions. induced-fit (IFD) results displayed strong affinities Chlordiazepoxide order IFD values −11.617, −10.599, −10.521, −9.988, respectively. research investigates Ioversol agents treatment rheumatoid arthritis (RA) they identified PAD4 inhibitors.

Language: Английский

Exploration of anti-inflammatory activity of pyrazolo[3,4-d]pyrimidine/1,2,4-oxadiazole hybrids as COX-2, 5-LOX and NO release inhibitors: Design, synthesis, in silico and in vivo studies DOI

M. Abdel Aziz,

Ibrahim M. Salem,

Mohammed A. AlAwadh

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 156, P. 108181 - 108181

Published: Jan. 22, 2025

Language: Английский

Citations

2
Microwave assisted synthesis, biological assessment and in-silico studies of some new 5,5′-(phenylmethylene)bisuracil and dihydropyrido[2,3-d:6,5-d']dipyrimidine derivatives as selective COX-2 inhibitors with potential anti-inflammatory activities DOI
Alaa M. Hayallah,

Mohamed A. Shaaban,

Mostafa Abdelrahman

et al.

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: unknown, P. 141504 - 141504

Published: Jan. 1, 2025

Language: Английский

Citations

1
From Bioinformatics to Clinical Application: A New Strategy in CRP Detection with Peptide Aptamer DOI
Xiaona Zhao, Tong Liu, Hongfang Chen

et al.

Journal of Pharmaceutical and Biomedical Analysis, Journal Year: 2025, Volume and Issue: unknown, P. 116820 - 116820

Published: March 1, 2025

Language: Английский

Citations

0
Anti-Inflammatory Activity of Two Labdane Enantiomers from Gymnosperma glutinosum: An In Vivo, In Vitro, and In Silico Study DOI Creative Commons
Salud Pérez‐Gutiérrez, Nimsi Campos‐Xolalpa,

Sofía A. Estrada-Barajas

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(4), P. 516 - 516

Published: April 1, 2025

Background/Objectives: Diseases associated with inflammatory processes continue to grow steadily throughout the world. Unfortunately, prolonged use of drugs induces adverse effects ranging from hypersensitivity reactions damage digestive system. These negative open possibility continuing search for anti-inflammatory compounds less toxicity. The aim this research was isolate and evaluate activity a mixture two enantiomeric labdanes isolated Gymnosperma glutinosum by in vivo, vitro, silico methods. Methods: A brief description main methods or treatments applied. This can include any relevant preregistration specimen information. structure enantiomers elucidated X-ray crystallography spectroscopies effect evaluated on mouse model ear edema induced 12-O-tetradecanoyl phorbol-13-acetate; pro-inflammatory mediators, nitric oxide (NO) interleukin (IL-6), were quantified macrophages stimulated lipopolysaccharide, interaction between diana studied molecular docking. Results: We identified chemical structures new labdane enantiomers: a-gymglu acid b-ent-gymglu acid. enantiomer mixture, named gymglu acid, diminished at doses 1 2 mg/ear 36.07% 41.99%, respectively. concentration 155.16 µM inhibited production NO 78.06% IL-6 71.04%. results suggest routes which these reduce inflammation: partial agonism toward corticosteroid receptors inhibition synthases. Conclusions: show that have promising activity.

Language: Английский

Citations

0
A Multifaceted Computational Approach to Identify PAD4 Inhibitors for the Treatment of Rheumatoid Arthritis (RA) DOI Creative Commons
Mansour S. Alturki, Mohamed S. Gomaa, Nada Tawfeeq

et al.

Metabolites, Journal Year: 2025, Volume and Issue: 15(3), P. 156 - 156

Published: Feb. 25, 2025

Background/Objectives: Neutrophil cells’ lysis forms the extracellular traps (NETs) to counter foreign body during insults body. Peptidyl arginine deiminase (PAD) participates in this process and is then released into fluid with lysed cell components. In some diseases, patients abnormal function of PADs, especially PAD 4, tend form autoantibodies against citrullinated proteins that are result activity on side chains. Those antibodies, which highly distinct RA, distinctly anti-citrullinated protein antibodies (ACPA). This study used an in-silico drug repurposing approach FDA-approved medications identify potential alternative can inhibit address solutions current limitations existing therapies. Methods: We utilized Maestro Schrödinger as a computational tool for preparing docking simulations 4 enzyme crystal structure retrieved from RCSB Protein Data Bank (PDB ID: 4X8G) while docked obtained Zinc 15 database. The was bound GSK 199—an investigational compound—as positive control molecules. Preparation performed by Wizard tool. Binding pocket determination Glide software (Schrödinger Release 2021–3:Schrödinger, LLC., New York, NY, USA, 2021). validation molecular carried out through redocking 199 superimposition. After that, standard induced fit were performed. Results/Conclusions: Among four hits Pemetrexed, Leucovorin, Chlordiazepoxide, Ioversol, showed highest XP scores providing favorable binding interactions. induced-fit (IFD) results displayed strong affinities Chlordiazepoxide order IFD values −11.617, −10.599, −10.521, −9.988, respectively. research investigates Ioversol agents treatment rheumatoid arthritis (RA) they identified PAD4 inhibitors.

Language: Английский

Citations

0