Investigation of inhibitory properties of some hydrazone compounds on hCA I, hCA II and AChE enzymes

Kucukoglu K., GÜL H. İ., TASLIMI P., GÜLÇİN İ., Supuran C. T.

BIOORGANIC CHEMISTRY, cilt.86, ss.316-321, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 86
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1016/j.bioorg.2019.02.008
  • Dergi Adı: BIOORGANIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.316-321
  • Anahtar Kelimeler: Hydrazone, Mannich base, Carbonic anhydrase, Acetylcholinesterase, Enzyme inhibition, MONO-MANNICH-BASES, CARBONIC-ANHYDRASE INHIBITORS, CORRESPONDING AZINE DERIVATIVES, ACETYLCHOLINE ESTERASE, BIOLOGICAL EVALUATION, HUMAN HEPATOMA, CYTOTOXICITY, ANTICANCER, PURIFICATION, BIOACTIVITY
  • Atatürk Üniversitesi Adresli: Evet

Özet

Recently, inhibition of carbonic anhydrase (hCA) and acetylcholinesterase (AChE) have appeared as a promising approach for pharmacological intervention in a variety of disorders such as glaucoma, epilepsy, obesity, cancer, and Alzheimer's disease. Keeping this in mind, N, N'-bis[(1-aryl-3-heteroaryl) propylidene] hydrazine dihydrochlorides, N1-N11, P1, P4-P8, and R1-R6, were synthesized to investigate their inhibitory activity against hCA I, hCA II, and AChE enzymes. All compounds in N, P, and R-series inhibited hCAs (I and II) and AChE more efficiently than the reference compounds acetazolamide (AZA), and tacrine. According to the activity results, the most effective inhibitory compounds were in R-series with the K-i values of 203 +/- 55-473 +/- 67 nM and 200 +/- 34-419 +/- 94 nM on hCA I, and hCA II, respectively. N, N'-Bis[1-(4-fluorophenyl)-3-(morpholine-4-yl) propylidene] hydrazine dihydrochlorides, N8, in N-series, N, N'-Bis[1-(4-hydroxyphenyl)-3-(piperidine-1-yl) pro-pylidene] hydrazine dihydrochlorides, P4, in P-series, and N, N'-bis[1-(4-chlorophenyl)-3-(pyrrolidine-1-yl) pro-pylidene] hydrazine dihydrochlorides, R5, in R-series were the most powerful compounds against hCA I with the K-i values of 438 +/- 65 nM, 344 +/- 64 nM, and 203 +/- 55 nM, respectively. Similarly, N8, P4, and R5 efficiently inhibited hCA II isoenzyme with the K-i values of 405 +/- 60 nM, 327 +/- 80 nM, and 200 +/- 34 nM, respectively. On the other hand, P-series compounds had notable inhibitory effect against AChE than the reference compound tacrine and the K-i values were between 66 +/- 20 nM and 128 +/- 36 nM. N, N'-Bis[1-(4-fluorophenyl)-3-(piperidine-1-yl) propylidene] hydrazine dihydrochlorides, P7, was the most potent compound on AChE with the K-i value of 66 +/- 20 nM. The other most promising compounds, N, N'-bis[1-(4-hydroxyphenyl)-3-(morpholine-4-yl) propylidene] hydrazine dihydrochlorides, N4 in N-series and N, N'-bis[1-(4-hydroxyphenyl)-3-(pyrrolidine-1-yl) propylidene] hydrazine dihydrochlorides, R4 in R-series were againts AChE with the K-i values of 119 +/- 20 nM, 88 +/- 14 nM, respectively.