Synthesis of beta-amino acid derivatives and their inhibitory profiles against some metabolic enzymes

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Atmaca U., Daryadel S., Taslimi P., Çelik M., Gülçin İ.

ARCHIV DER PHARMAZIE, cilt.352, sa.12, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 352 Sayı: 12
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1002/ardp.201900200
  • Dergi Adı: ARCHIV DER PHARMAZIE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Anahtar Kelimeler: acetylcholinesterase, carbonic anhydrase, enzyme inhibition, alpha-glycosidase, beta-amino acid, CARBONIC-ANHYDRASE INHIBITORS, ERYTHROCYTE ISOZYMES I, ISOENZYMES HCA I, BIOLOGICAL EVALUATION, CRYSTAL-STRUCTURE, ANTICHOLINERGIC ACTIVITIES, ACETYLCHOLINE ESTERASE, 1ST SYNTHESIS, POTENT, ANTIOXIDANT
  • Atatürk Üniversitesi Adresli: Evet

Özet

Sulfamate and its derivatives have a range of biological activities. One-pot cyclocondensation of alkenes (1a-i) with chlorosulfonyl isocyanate generates beta-lactams. beta-Amino acid derivatives (2a-i) from beta-lactams were synthesized. Then, these highly reactive compounds were opened with MeOH to produce the corresponding sulfamate derivatives in good yields. The inhibitory effects of the novel sulfamate derivatives were tested on human carbonic anhydrase I and II isoenzymes (hCA I and hCA II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and alpha-glycosidase (alpha-Gly). Novel sulfamate derivatives showed K-i values in the range of 23.81-42.97 nM against hCA I, 8.95-52.23 nM against hCA II, 8.10-45.51 nM against AChE, 23.16-81.84 nM against BChE, and 14.02-48.68 nM against alpha-Gly. As a result, the novel sulfamate derivatives had potent inhibitory effects against both isoenzymes. Overall, due to the inhibitory effects of the novel sulfamate derivatives on the tested metabolic enzymes, they are promising drug candidates for the treatment of diseases like glaucoma, epilepsy, leukemia, Alzheimer's disease, and type 2 diabetes mellitus, which are associated with high enzymatic activity of the indicated metabolic enzymes.