1,3-Disubstituted urea derivatives: Synthesis, antimicrobial activity evaluation and in silico studies

GÜNDÜZ M. G., Uğur S. B., Güney F., Özkul C., Krishna V. S., Kaya S., ...Daha Fazla

BIOORGANIC CHEMISTRY, cilt.102, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 102
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1016/j.bioorg.2020.104104
  • Dergi Adı: BIOORGANIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: Antibacterial, Tuberculosis, Antifungal, Biofilm, Molecular docking, Quorum sensing, PSEUDOMONAS-AERUGINOSA, BIOFILM FORMATION, DRUG DISCOVERY, DOCKING, UPDATE
  • Hacettepe Üniversitesi Adresli: Evet

Özet

The development of new antimicrobial compounds is in high demand to overcome the emerging drug resistance against infectious microbial pathogens. In the present study, we carried out the extensive antimicrobial screening of disubstituted urea derivatives. In addition to the classical synthesis of urea compounds by the reaction of amines and isocyanates, we also applied a new route including bromination, oxidation and azidination reactions, respectively, to convert 2-amino-3-methylpyridine to 1,3-disubstituted urea derivatives using various amines. The evaluation of antimicrobial activities against various bacterial strains, Candida albicans as well as Mycobacterium tuberculosis resulted in the discovery of new active molecules. Among them, two compounds, which have the lowest MIC values on Pseudomonas aeruginosa, were further evaluated for their inhibition capacities of biofilm formation. In order to evaluate their potential mechanism of biofilm inhibition, these two compounds were docked into the active site of LasR, which is the transcriptional regulator of bacterial signaling mechanism known as quorum sensing. Finally, the theoretical parameters of the bioactive molecules were calculated to establish their drug-likeness properties.