Synthesis, molecular dynamics simulation, and evaluation of biological activity of novel flurbiprofen and ibuprofen-like compounds

Yildiz M. T., OSMANİYE D., SAĞLIK ÖZKAN B. N., LEVENT S., Kurnaz R., ÖZKAY Y., ...Daha Fazla

JOURNAL OF MOLECULAR RECOGNITION, cilt.37, sa.5, 2024 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 37 Sayı: 5
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1002/jmr.3089
  • Dergi Adı: JOURNAL OF MOLECULAR RECOGNITION
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, Communication Abstracts, MEDLINE, Metadex, Civil Engineering Abstracts
  • Anahtar Kelimeler: COX-1 inhibitors, flurbiprofen, ibuprofen, molecular dynamics simulation, phenylacetic acid
  • Anadolu Üniversitesi Adresli: Evet

Özet

The frequent use of anti-inflammatory drugs and the side effects of existing drugs keep the need for new compounds constant. For this purpose, flurbiprofen and ibuprofen-like compounds, which are frequently used anti-inflammatory compounds in this study, were synthesized and their structures were elucidated. Like ibuprofen and flurbiprofen, the compounds contain a residue of phenylacetic acid. On the other hand, it contains a secondary amine residue. Thus, it is planned to reduce the acidity, which is the biggest side effect of NSAI drugs, even a little bit. The estimated ADME parameters of the compounds were evaluated. Apart from internal use, local use of anti-inflammatory compounds is also very important. For this reason, the skin permeability values of the compounds were also calculated. And it has been found to be compatible with reference drugs. The COX enzyme inhibitory effects of the obtained compounds were tested by in vitro experiments. Compound 2a showed significant activity against COX-1 enzyme with an IC50 = 0.123 + 0.005 mu M. The interaction of the compound with the enzyme active site was clarified by molecular dynamics studies.