New anticancer drug candidates sulfonamides as selective hCA IX or hCA XII inhibitors

GÜL H. İ., YAMALI C., Sakagami H., ANGELİ A., LEİTANS J., KAZAKS A., ...Daha Fazla

BIOORGANIC CHEMISTRY, cilt.77, ss.411-419, 2018 (SCI-Expanded) identifier identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 77
  • Basım Tarihi: 2018
  • Doi Numarası: 10.1016/j.bioorg.2018.01.021
  • Dergi Adı: BIOORGANIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.411-419
  • Anahtar Kelimeler: Pyrazoline, Sulfonamide, Anticancer, Carbonic anhydrases, Dental cells, CARBONIC-ANHYDRASE INHIBITORS, HETEROCYCLIC SULFONAMIDES, BIOLOGICAL EVALUATION, CANCER, DERIVATIVES, CYTOTOXINS, BENZENESULFONAMIDES, BIOACTIVITIES, CHALCONES, APOPTOSIS
  • Atatürk Üniversitesi Adresli: Evet

Özet

In this study, new 4-13-(aryl)-5-substitutedphenyl-4,5-dihydro-1H-pyrazole-1-yllbenzensulfonamides (19-36) were synthesized and evaluated their cytotoxic/anticancer and CA inhibitory effects. According to results obtained, the compounds 34 (4-[5-(2,3,4-trimethoxyphenyl)-3-(thiophen-2-yl)4,5-dihydro-1H-pyrazole-1-yl benzensulfonamide, Potency-Selectivity Expression (PSE) = 141) and 36 (44 543,4,5-trimethoxyphenyl)-3-( thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-yl benzensulfonamide, PSE = 54.5) were found the leader anticancer compounds with the highest PSE values. In CA inhibitory studies, the compounds 36 and 24 (4-[5-(3,4,5-trimethoxyphenyl) 3 (4 fluorophenyl)-4,5-dihydro-1H-pyrazole-1-yl]benzensulfonamide) were found the leader CA inhibitors depending on selectivity ratios. The compound 36 was a selective inhibitor of hCA XII isoenzyme (hCA l/hCA XII = 1250 and hCA II/hCA XII = 224) while the compound 24 was a selective inhibitor of hCA IX isoenzyme (hCA l/hCA IX = 161 and hCA II/hCA IX = 177). The compounds 24, 34, and 36 can be considered to develop new anticancer drug candidates. (C) 2018 Elsevier Inc. All rights reserved.