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

GÜL H. İ. , Yamali C. , Sakagami H., Angeli A., Leitans J., Kazaks A., ...Daha Fazla

BIOORGANIC CHEMISTRY, cilt.77, ss.411-419, 2018 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 77
  • Basım Tarihi: 2018
  • Doi Numarası: 10.1016/j.bioorg.2018.01.021
  • Sayfa Sayıları: ss.411-419


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.