Discovery of 3-hydroxy-3-pyrrolin-2-one-based mPGES-1 inhibitors using a multi-step virtual screening protocol
| Autor: | Giuseppe Bifulco, Oliver Werz, Katrin Fischer, Andreas Koeberle, Vincenza Cantone, Marianna Potenza, Gianluigi Lauro, Raffaele Riccio |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pharmacology Virtual screening Chemistry Organic Chemistry Pharmaceutical Science Biological activity Computational biology Shape alignment Ligand (biochemistry) Biochemistry 03 medical and health sciences 030104 developmental biology Qualitative analysis Drug Discovery Molecular Medicine lipids (amino acids peptides and proteins) Protocol (object-oriented programming) |
| Zdroj: | MedChemComm. 9:2028-2036 |
| ISSN: | 2040-2511 2040-2503 |
| DOI: | 10.1039/c8md00497h |
| Popis: | Targeting microsomal prostaglandin E(2) synthase-1 (mPGES-1) represents an efficient strategy for the development of novel drugs against inflammation and cancer with potentially reduced side effects. With this aim, a virtual screening was performed on a large library of commercially available molecules using the X-ray structure of mPGES-1 co-complexed with a potent inhibitor. Combining fast ligand-based shape alignment, molecular docking experiments, and qualitative analysis of the binding poses, a small set of molecules was selected for the subsequent steps of validation of the biological activity. Compounds 2 and 3, bearing the 3-hydroxy-3-pyrrolin-2-one nucleus, showed mPGES-1-inhibitory activity in the low micromolar range. These data highlighted the applicability of the reported virtual screening protocol for the selection of new mPGES-1 inhibitors as promising anti-inflammatory/anti-cancer drugs. |
| Databáze: | OpenAIRE |
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