Metal-Free Synthesis via Intramolecular Cyclization, Enzyme Inhibition Properties and Molecular Docking of Novel Isoindolinones

Atmaca U., Saglamtas R., Sert Y., Çelik M., Gülçin İ.

ChemistrySelect, cilt.8, sa.9, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 8 Sayı: 9
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1002/slct.202204578
  • Dergi Adı: ChemistrySelect
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier
  • Anahtar Kelimeler: Isoindolinone, Sulfamate, alpha-Glycosidase, Carbonic anhydrase, Acetylcholinesterase, CARBONIC-ANHYDRASE INHIBITION, ALPHA-GLUCOSIDASE INHIBITORS, TROUT ONCORHYNCHUS-MYKISS, ERYTHROCYTE ISOZYMES I, BIOLOGICAL EVALUATION, CRYSTAL-STRUCTURE, ISOENZYMES I, ACETYLCHOLINESTERASE, DERIVATIVES, BUTYRYLCHOLINESTERASE
  • Atatürk Üniversitesi Adresli: Evet

Özet

Highly effective one-pot synthesis of novel isoindolinones from various 2-benzoylbenzoic acid derivatives with intramolecular cyclization in the presence of chlorosulfonyl isocyanate was reported in mild conditions in the absence a metal catalyst. Novel synthesized compounds were tested against some metabolic enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glycosidase and carbonic anhydrase I and II (hCA I and hCA II) enzymes that associated with Alzheimer's disease (AD), type-2 diabetes mellitus (T2DM), epilepsy, and glaucoma. A series of novel isoindolinones (2 a–l) were evaluated as highly potent inhibition ability toward AChE (Kis: 2.33–13.81 μM), BChE (Kis: 1.45–12.27 μM), α-glycosidase (Kis: 8.03–23.05 μM), hCA I (Kis: 2.23–17.35 μM) and hCA II (Kis: 2.86–18.13 μM). Also, for these inhibitors, in silico molecular docking simulations and calculations were done with the Autodock Vina program to support the in vitro experimental studies.