A novel D-limonene derivative: synthesis, characterization, molecular docking, molecular dynamics and ADMET prediction studies

Fawzi M., Laamari Y., Oubella A., Rehman M. T., Sahin E., Fahad AlAjmi M., ...Daha Fazla

Journal of Sulfur Chemistry, 2024 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1080/17415993.2024.2375308
  • Dergi Adı: Journal of Sulfur Chemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, Chimica
  • Anahtar Kelimeler: ADMET, D-limonene, Isoxazole, Molecular docking, Molecular dynamics, Thiazolidinone, Topoisomerase IIα
  • Ankara Üniversitesi Adresli: Evet

Özet

Synthesis, characterization, and theoretical studies of a novel limonene-bis(isoxazole)-thiazolidinone hybrid, prepared from natural D-limonene in five steps, were conducted. The compounds obtained were successfully identified using HRMS, 1H- and 13C-NMR spectral data. Subsequently, in-silico docking and molecular dynamic simulation studies were performed to predict potential interaction modes between the compounds and the active sites of the target hTopo IIα. Both studies indicated that all molecules exhibited good binding affinity towards the hTopo IIα enzyme, similar to the reference drug etoposide, when placed in the enzyme’s active site. In addition, in silico ADME/Tox studies were carried out to assess the drug-likeness and pharmacokinetic properties of the molecules. The limonene-bis(isoxazole)-thiazolidinone hybrid derivatives may serve as promising lead compounds for the development of new topoisomerase-targeted anticancer agents.