Synthesis and bioactivities of pyrazoline benzensulfonamides as carbonic anhydrase and acetylcholinesterase inhibitors with low cytotoxicity

Ozgun D. O., GÜL H. İ., YAMALI C., Sakagami H., GÜLÇİN İ., Sukuroglu M. K., ...Daha Fazla

BIOORGANIC CHEMISTRY, cilt.84, ss.511-517, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 84
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1016/j.bioorg.2018.12.028
  • Dergi Adı: BIOORGANIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.511-517
  • Anahtar Kelimeler: Sulfonamide, Pyrazoline, Cytotoxicity, Carbonic anhydrase, Acetylcholinesterase, BIOLOGICAL EVALUATION, MOLECULAR DOCKING, MANNICH-BASES, HCA IX, APOPTOSIS, DERIVATIVES, CHALCONES, CHOLINESTERASE, SULFONAMIDES, PATHWAYS
  • Gazi Üniversitesi Adresli: Evet

Özet

4-(3-Substitutedphenyl-5-polymethoxyphenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamides (9-16) were synthesized and their chemical structures were elucidated by H-1 NMR, C-13 NMR, and HRMS. The compounds designed include pyrazoline and sulfonamide pharmacophores in a single molecule by hibrit molecule approach which is a useful technique in medicinal chemistry in designing new compounds with potent activity for the desired several bioactivities. Inhibition potency of the sulfonamides were evaluated against human CA isoenzymes (hCA I and hCA II) and acetylcholinesterase (AChE) enzyme and also their cytotoxicities were investigated towards oral squamous cancer cell carcinoma (OSCC) cell lines (Ca9-22, HSC-2, HSC-3, and HSC-4) and non-tumor cells (HGF, HPLF, and HPC). Cytosolic hCA I and hCA II isoenzymes were inhibited by the sulfonamide derivatives (9-16) and Ki values were found in the range of 27.9 +/- 3.2-74.3 +/- 28.9 nM and 27.4 +/- 1.4-54.5 +/- 11.6 nM, respectively. AChE enzyme was strongly inhibited by the sulfonamide derivatives with Ki values in the range of 37.7 +/- 14.4-89.2 +/- 30.2 nM The CC50 values of the compounds were found between 15 and 200 mu M towards OSCC malign cell lines. Their tumor selectivities were also calculated with two ways. Compound's selectivities towards cancer cell line were found generally low, except compounds bearing 3,4-dimethoxyphenyl 14 (TS1 = 1.3, TS2 = 1.4) and 10 (TS2 = 1.4). All sulfonamide derivatives studied here can be considered as good candidates to develop novel CAs or AChE inhibitor candidates based on the enzyme inhibition potencies with their low cytotoxicity and tumor selectivity.