Synthesis and some enzyme inhibition effects of isoxazoline and pyrazoline derivatives including benzonorbornene unit

Yavari M. A., Adiloglu Y., Saglamtas R., TUTAR A., GÜLÇİN İ., MENZEK A.

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, cilt.36, sa.2, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 36 Sayı: 2
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1002/jbt.22952
  • Dergi Adı: JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Agricultural & Environmental Science Database, Applied Science & Technology Source, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Food Science & Technology Abstracts, MEDLINE
  • Anahtar Kelimeler: 1, 3-dipolar cycloaddition, acetylcholinesterase, butyrylcholinesterase, enzyme inhibition, isoxazoline, pyrazoline, HIGH-TEMPERATURE BROMINATION, CARBONIC-ANHYDRASE, CRYSTAL-STRUCTURE, REARRANGEMENT REACTIONS, CYCLOADDITION REACTIONS, NATURAL-PRODUCTS, 1ST SYNTHESIS, ACETYLCHOLINESTERASE, BROMOPHENOLS, ANTIOXIDANT
  • Atatürk Üniversitesi Adresli: Evet

Özet

Four new and four known isoxazoline derivatives were synthesized from the reactions of benzonorbornadiene with nitrile oxides formed from the corresponding benzaldehydes. Three new and one known pyrazoline derivatives were also synthesized from the reactions of the benzonorbornadiene with nitrile imines formed from the corresponding compounds. The synthesized nitrogen-based novel heterocyclic compounds were evaluated against the human carbonic anhydrase isoenzymes I and II (hCA I and hCA II), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes. The synthesized nitrogen-based novel heterocyclic compounds showed IC50 values in the range of 2.69-7.01 against hCA I, 2.40-4.59 against hCA II, 0.81-1.32 mu M against AChE, and 20.83-1.70 mu M against BChE enzymes. On the contrary, nitrogen-based novel heterocyclic compounds demonstrated K-i values between 2.93 +/- 0.59-8.61 +/- 1.39 against hCA I, 2.05 +/- 0.62-4.97 +/- 0.95 against hCA II, 0.34 +/- 0.02-0.92 +/- 0.17 nM against AChE, and 0.50 +/- 0.04-1.20 +/- 0.16 mu M against BChE enzymes. The synthesized nitrogen-based novel heterocyclic compounds exhibited effective inhibition profiles against both indicated metabolic enzymes. These results may contribute to the development of new drugs particularly to treat some disorders, which are widespread in the world including glaucoma and Alzheimer's diseases.