Organohalogen chalcones: design, synthesis, ADMET prediction, molecular dynamics study and inhibition effect on acetylcholinesterase and carbonic anhydrase

Aydin B. O., ANIL D., Demir Y., ALAGÖZ M. A.

Molecular Diversity, 2024 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1007/s11030-023-10774-9
  • Dergi Adı: Molecular Diversity
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, MEDLINE
  • Anahtar Kelimeler: Acetylcholinesterase, ADMET, Carbonic anhydrase, Organohalogen chalcone
  • Atatürk Üniversitesi Adresli: Evet

Özet

In an effort to discover potential acetylcholinesterase (AChE) and carbonic anhydrase (CA) inhibitors, a novel series of organohalogen chalcone derivatives (12–20, 23–30) was synthesized, and their chemical structures were characterized by spectral analysis. They showed a highly potent inhibition effect on AChE and hCAs (Ki values range from 5.07 ± 0.062 to 65.53 ± 4.36 nM for AChE, 13.54 ± 2.55 to 94.11 ± 10.39 nM for hCA I, and 5.21 ± 0.54 to 57.44 ± 3.12 nM for hCA II). In addition, the chalcone derivatives with the highest inhibitor score docked into the active site of the indicated metabolic enzyme receptors, and their absorption, metabolism, and toxic properties were evaluated according to ADMET's estimation.Compounds 16 and 19 exhibited the highest inhibition score, emerged as lead compounds, and inspired the development of more potent compounds.