2H-Indazolo[2,1-b]phthalazine-trione derivatives: Inhibition on some metabolic enzymes and molecular docking studies

Taslimi P., Türkan F., TURHAN K., Karaman H. S., TURGUT Z., GÜLÇİN İ.

Journal of Heterocyclic Chemistry, cilt.57, sa.8, ss.3116-3125, 2020 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 57 Sayı: 8
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1002/jhet.4019
  • Dergi Adı: Journal of Heterocyclic Chemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), Chimica, EMBASE
  • Sayfa Sayıları: ss.3116-3125
  • Atatürk Üniversitesi Adresli: Evet

Özet

In this study, substituted 2H-indazolo[2,1-b]phthalazine-1,6,11-trione compounds (4a-d) obtained via one-pot three-component condensation reaction of aromatic aldehydes, cyclic 1,3-dione, and phthalhydrazide in ethanol catalyzed by Y(OTf)(3) showed satisfactory inhibitory effects against some important enzymes. Also, these molecules had K-i values in the row of 185.92 +/- 36.03-294.82 +/- 50.76 nM vs carbonic anhydrase I (CA I), 204.93 +/- 46.90-374.10 +/- 83.63 nM against human CA II, 937.16 +/- 205.82-1021.83 +/- 193.66 nM against alpha-glycosidase (alpha-Gly), respectively. For cholinesterase enzymes, the K-i values were found in the range of 47.26 +/- 9.62-72.05 +/- 19.47 nM against acetylcholinesterase (AChE) and 65.03 +/- 9.88-102.83 +/- 25.04 nM against butyrylcholinesterase (BChE), respectively. The inhibition effects of these compounds against enzymes whose name are AChE, BChE, alpha-Gly, hCA I, and hCA II, were compared with control molecules like tacrine, acarbose, and acetazolamide.