Synthesis, biological evaluation and in silico studies of novel N-substituted phthalazine sulfonamide compounds as potent carbonic anhydrase and acetylcholinesterase inhibitors

TÜRKEŞ C., Arslan M., Demir Y., Çoçaj L., Rifati Nixha A., BEYDEMİR Ş.

Bioorganic Chemistry, cilt.89, 2019 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 89
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1016/j.bioorg.2019.103004
  • Dergi Adı: Bioorganic Chemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Anahtar Kelimeler: Acetylcholinesterase, Carbonic anhydrase, Enzyme inhibitors, Molecular docking, Phthalazine, Sulfonamide
  • Bilecik Şeyh Edebali Üniversitesi Adresli: Evet

Özet

The synthesis, characterization and biological evaluation of a series of novel N-substituted phthalazine sulfonamide (5a-l) are disclosed. Phthalazines which are nitrogen-containing heterocyclic compounds are biologically preferential scaffolds, endowed with versatile pharmacological activity, such as anti-inflammatory, cardiotonic vasorelaxant, anticonvulsant, antihypertensive, antibacterial, anti-cancer action. The compounds were investigated for the inhibition against the cytosolic hCA I, II and AChE. Most screened sulfonamides showed high potency in inhibiting hCA II, widely involved in glaucoma, epilepsy, edema, and other pathologies (Kis in the ranging from 6.32 ± 0.06 to 128.93 ± 23.11 nM). hCA I was inhibited with Kis in the range of 6.80 ± 0.10–85.91 ± 7.57 nM, whereas AChE in the range of 60.79 ± 3.51–249.55 ± 7.89 nM. ADME prediction study of the designed N-substituted phthalazine sulfonamides showed that they are not only with carbonic anhydrase and acetylcholinesterase inhibitory activities but also with appropriate pharmacokinetic, physicochemical parameters and drug-likeness properties. Also, in silico docking studies were investigated the binding modes of selected compounds, to hCA I, II, and AChE.