Synthesis and In vitro Evaluation of Thiadiazole Derivatives as AChE, BuChE and LOX Inhibitors

ALTINTOP M. D., ÖZDEMİR A., Abu Mohsen U., TEMEL H. E., AKALIN ÇİFTÇİ G., KAPLANCIKLI Z. A.

LETTERS IN DRUG DESIGN & DISCOVERY, cilt.11, sa.9, ss.1062-1069, 2014 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 11 Sayı: 9
  • Basım Tarihi: 2014
  • Doi Numarası: 10.2174/1570180811666140529004517
  • Dergi Adı: LETTERS IN DRUG DESIGN & DISCOVERY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1062-1069
  • Anahtar Kelimeler: Acetylcholinesterase, butyrylcholinesterase, lipoxygenase, thiadiazole, ALZHEIMERS-DISEASE, CHOLINESTERASE-INHIBITORS, BIOLOGICAL-ACTIVITIES, 1,3,4-THIADIAZOLE
  • Anadolu Üniversitesi Adresli: Evet

Özet

N'-Benzylidene-2-[[5-(phenylamino)-1,3,4-thiadiazol-2-yl]thio]acetohydrazide derivatives (5a-p) were synthesized to screen for their AChE, BuChE and LOX inhibitory activity. The CCK-8 assay was also carried out to determine their cytotoxicity against NIH/3T3 cells. The most potent AChE inhibitors were found as compounds 5m (49.79% +/- 3.08) and 5p (42.39% +/- 3.19), whereas the most potent BuChE inhibitor was found as compound 5d (35.15% +/- 2.21). Among these derivatives, N'-(3-methoxybenzylidene)-2-[[5-(phenylamino)-1,3,4-thiadiazol-2-yl]thio]acetohydrazide (5p) can be considered as the most promising AChE inhibitor due to its low cytotoxicity to NIH/3T3 cells (IC50 > 500 mu g/mL). N'-(4-Methoxybenzylidene)- 2-[[5-(phenylamino)-1,3,4-thiadiazol-2-yl]thio]a-cetohydrazide (5n) exhibited weak inhibition on LOX (% 20.65 +/- 0.08), whilst the other compounds were not active.