Detection of Microsomal Prostaglandin E Syntase-1 (mPGES-1) Inhibitors by Structural Based Virtual Screening and Investigation as In Vitro

5th International Eurasian Conference on Biological and Chemical Sciences, Ankara, Türkiye, 23 - 25 Kasım 2022, ss.1664, (Özet Bildiri)

Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible prostaglandin E synthase after exposure to pro-

inflammatory stimuli. The mPGES-1 enzyme represents a new target for the therapeutic treatment of acute and chronic

inflammatory disorders and cancer. New mPGES-1 inhibitors should be determined for the purpose of drug design and

discovery aiming to develop new generation anti-inflammatory drugs.[1] For this purpose, compounds containing indole

scaffolds (30000) were downloaded from the Zinc-15 database, their 2D structures were converted to 3D and their

different conformations were obtained. The interactions between mPGES-1 and compounds with an indol scaffold were

determined by structure-based virtual scanning. These interactions were examined and ZINC000002639093 (compound

8) and ZINC000003323374 (compound 9) targeting the active site of mPGES-1 were selected as potential target

inhibitors. Molecular dynamics simulations of the reference and the two best compounds were performed to analyze the

dynamics between protein-ligand complexes. The antiproliferative effects of two selected target compounds in lung

cancer cells and their anti-inflammatory effects were determined by measuring the PGE2 levels formed in these cells. In

vitro experiments found that two compounds targeting the active site of mPGES-1 could be potential novel inhibitors.