Synthesis and Biological Evaluation of 2,3,4-Triaryl-1,2,4-oxadiazol-5-ones as p38 MAPK Inhibitors

Roberto Romeo; Salvatore V Giofrè; Maria A Chiacchio; Lucia Veltri; Consuelo Celesti; Daniela Iannazzo

doi:10.3390/molecules26061745

Synthesis and Biological Evaluation of 2,3,4-Triaryl-1,2,4-oxadiazol-5-ones as p38 MAPK Inhibitors

Molecules. 2021 Mar 20;26(6):1745. doi: 10.3390/molecules26061745.

Authors

Roberto Romeo¹, Salvatore V Giofrè¹, Maria A Chiacchio², Lucia Veltri³, Consuelo Celesti⁴, Daniela Iannazzo⁴

Affiliations

¹ Dipartimento di ScienzeChimiche, Biologiche, Farmaceutiche ed Ambientali, Università di Messina, Via S.S. Annunziata, 98168 Messina, Italy.
² DipartimentoScienze del Farmaco, Università di Catania, Viale A. Doria 6, 95125 Catania, Italy.
³ Dipartimento di Chimica e TecnologieChimiche, Universitàdella Calabria, Via P. Bucci 12/C, 87036 Arcavacata di Rende, Italy.
⁴ Dipartimento di Ingegneria, Università di Messina, Contrada Di Dio, 98166 Messina, Italy.

Abstract

A series of azastilbene derivatives, characterized by the presence of the 1,2,4-oxadiazole-5-one system as a linker of the two aromatic rings of stilbenes, have been prepared as novel potential inhibitors of p38 MAPK. Biological assays indicated that some of the synthesized compounds are endowed with good inhibitory activity towards the kinase. Molecular modeling data support the biological results showing that the designed compounds possess a reasonable binding mode in the ATP binding pocket of p38α kinase with a good binding affinity.

Keywords: 1,2,4-oxazolidinyl-5-ones; p38 MAPK inhibitors; stilbene analogs.

MeSH terms

Drug Design
Drug Evaluation, Preclinical
Humans
Molecular Docking Simulation*
Protein Kinase Inhibitors* / chemical synthesis
Protein Kinase Inhibitors* / chemistry
Structure-Activity Relationship
p38 Mitogen-Activated Protein Kinases* / antagonists & inhibitors
p38 Mitogen-Activated Protein Kinases* / chemistry

Substances

Protein Kinase Inhibitors
p38 Mitogen-Activated Protein Kinases