Designing heterocyclic chalcones, benzoyl/sulfonyl hydrazones: An insight into their biological activities and molecular docking study


Kurşun Aktar B. S., Sıcak Y., Tok T. T., Oruç-Emre E. E., Yağlıoğlu A. Ş., Iyidoğan A. K., ...Daha Fazla

Journal of Molecular Structure, cilt.1211, 2020 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1211
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1016/j.molstruc.2020.128059
  • Dergi Adı: Journal of Molecular Structure
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chimica, Compendex, INSPEC
  • Anahtar Kelimeler: Anticholinesterase activity, Antioxidant activity, Antiproliferative activity, Chalcone, Hydrazone, Molecular docking
  • Ondokuz Mayıs Üniversitesi Adresli: Hayır

Özet

The aim of this study is to investigate the antioxidant, anticholinesterase and the antiproliferative activities of some chalcones, benzoyl and sulfonyl hydrazones. The antioxidant activity was studied by way of four complimentary assays and the anticholinesterase activity was studied using the Ellman method. The antiproliferative activity of the compounds was determined using a BrdU cell proliferation ELISA assay. Compound 32 (IC50: 15.58 ± 0.01 μg/mL) against the brain (C6) and 29 (IC50: 5.02 ± 0.05 μg/mL) against cervical (HeLa) cancer cell lines exhibited higher antiproliferative activity than the other compounds. Two sulfonyl hydrazone derivatives 45 and 47 exhibited very good antioxidant activity. The results of anticholinesterase activity indicated that nine compounds 3, 8, 10, 14, 24, 25, 27, 38, and 45 significantly inhibited acetylcholinesterase enzymes and thirty-three compounds 1–4, 7–14, 22–28, 32–41, 44–47 inhibited butyrylcholinesterase enzymes (BChE) more than galantamine. In addition, virtual screening methods based on ligand 45 having the best activity against BChE was used to define new human BChE inhibitors. The interactions of ligand 8 against acetylcholinesterase (AChE) were also examined. Important key residues were determined and visualized on completion of the methodology. All calculations indicated the suitability of use of the molecular docking approach for understanding interaction mechanisms and crucial fragments of novel hit compounds such as the potential lead AChE and BChE inhibitor candidates.