Fragment Pharmacophore-Based Screening: An Efficient Approach for Discovery of New Inhibitors of Toll-Like Receptor 5

Title:Fragment Pharmacophore-Based Screening: An Efficient Approach for Discovery of New Inhibitors of Toll-Like Receptor 5

Volume: 19 Issue: 10

Author(s): Hoora Hashemi, Malihe Hassanzadeh and Massoud Amanlou

Affiliation:

Keywords: Fragment-based, molecular docking, pharmacophore model, TLR5, virtual screening, molecular dynamics.

Abstract: Aim and objective: Rheumatoid Arthritis (RA) is a progressing autoimmune inflammatory disease of joint, hallmarked by inflammation, pain and atrophy of bones. Toll-like receptor 5 (TLR5) is a novel inflammatory mediator in RA, and TLR5 inhibitors are speculated to have a therapeutic potential for the treatment of RA.

Material and method: Here we applied fragment pharmacophore-based virtual screening to identify novel TLR5 ligands.

Results: Among compounds collected from Otava peptidomimetic compounds, Maybridge fragment and ZINC libraries, 3355 compounds were selected for docking into the flagellin-binding site of TLR5. 16 compounds with the required interaction, critical amino acid residues and the binding free energies <-7 kcal/mol were identified as potential TLR5 inhibitors, one of which was followed up by molecular dynamics simulation.

Conclusion: These compounds open a possibility to discover novel TLR5 inhibitors for the treatment of RA.

Cite this article as:

Hashemi Hoora, Hassanzadeh Malihe and Amanlou Massoud, Fragment Pharmacophore-Based Screening: An Efficient Approach for Discovery of New Inhibitors of Toll-Like Receptor 5, Combinatorial Chemistry & High Throughput Screening 2016; 19 (10) . https://dx.doi.org/10.2174/1386207319666160907103507

DOI https://dx.doi.org/10.2174/1386207319666160907103507	Print ISSN 1386-2073
Publisher Name Bentham Science Publisher	Online ISSN 1875-5402