Synthesis and Biological Evaluation of Pyrimidine-oxazolidin-2-arylimino Hybrid Molecules as Antibacterial Agents

• Main Authors: Roberto Romeo, Maria A. Chiacchio, Agata Campisi, Giulia Monciino, Lucia Veltri, Daniela Iannazzo, Gianluigi Broggini, Salvatore V. Giofrè
• Format: Article
• Language: English
• Published: MDPI AG 2018-07-01
• Series: Molecules
• Subjects: intramolecular alkoxyhalogenation; Suzuki coupling; antibacterial compounds; pyrimidine-oxazolidinone hybrids; molecular docking
• Online Access: http://www.mdpi.com/1420-3049/23/7/1754

Pyrimidine-1,3-oxazolidin-2-arylimino hybrids have been synthesized as a new class of antibacterial agents. The synthetic approach exploits a Cu(II)-catalyzed intramolecular halkoxyhalogenation of alkynyl ureas, followed by a Suzuki coupling reaction with 2,4-dimethoxypyrimidin-5-boronic acid. Biological screenings revealed that most of the compounds showed moderate to good activity against two Gram-positive (B. subtilis, S. aureus) and three Gram-negative (P. aeruginosa, S. typhi, K. pneumonia) pathogenic strains. A molecular docking study, performed in the crystal structure of 50S ribosomal unit of Haloarcula marismortui, indicated that pyrimidine-oxazolidin-2-arylimino hybrids 8c and 8h exhibited a high binding affinity (−9.65 and −10.74 kcal/mol), which was in agreement with their good antibacterial activity. The obtained results suggest that the combination of pyrimidine and oxazolidone moieties can be considered as a valid basis to develop new further modifications towards more efficacious antibacterial compounds.