2,3-Dihydrobenzofuran privileged structures as new bioinspired lead compounds for the design of mPGES-1 inhibitors

Simone Di Micco (1) , Carmela Spatafora (2) , Nunzio Cardullo (2) , Raffaele Riccio (1) , Katrin Fischer (3) , Carlo Pergola (3) , Andreas Koeberle (3) , Oliver Werz (3) , Malik Chalal (4) , Dominique Vervandier-Fasseur (4) , Corrado Tringali (2) , Giuseppe Bifulco (1)

1 UNISA - Università degli Studi di Salerno = University of Salerno
2 dipartimento di scienze chimiche
3 Department of Pharmaceutical/Medicinal Chemistry
4 ICMUB - Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon]

2,3-Dihydrobenzofurans are proposed as privileged structures and used as chemical platform to design small compound libraries. By combining molecular docking calculations and experimental verification of biochemical interference, we selected some potential inhibitors of microsomal prostaglandin E2 synthase (mPGES)-1. Starting from low affinity natural product 1, by our combined approach we identified the compounds 19 and 20 with biological activity in the low micromolar range. Our data suggest that the 2,3-dihydrobenzofuran derivatives might be suitable bioinspired lead compounds for development of new generation mPGES-1 inhibitors with increased affinity.

Mots clés: 2; 3-Dihydrobenzofuran privileged structure; Cancer; Inflammation; Molecular docking; mPGES-1 inhibitors

Domaines: Chimie; Cancer

Simone Di Micco, Carmela Spatafora, Nunzio Cardullo, Raffaele Riccio, Katrin Fischer, et al.. 2,3-Dihydrobenzofuran privileged structures as new bioinspired lead compounds for the design of mPGES-1 inhibitors. Bioorganic and Medicinal Chemistry, 2016, 24 (4), pp.820 - 826. ⟨10.1016/j.bmc.2016.01.002⟩. ⟨hal-01390150⟩