Investigation of carbonic anhydrase inhibitory effects and cytotoxicities of pyrazole-based hybrids carrying hydrazone and zinc-binding benzenesulfonamide pharmacophores

YAMALI C., Sakagami H., Satoh K., Bandow K., Uesawa Y., Bua S., ...Daha Fazla

Bioorganic Chemistry, cilt.127, 2022 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 127
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1016/j.bioorg.2022.105969
  • Dergi Adı: Bioorganic Chemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: Anticancer, Benzenesulfonamide, Carbohydrazone, Carbonic anhydrase, hCA IX, OSCC, Pyrazole
  • Atatürk Üniversitesi Adresli: Evet

Özet

© 2022 Elsevier Inc.Pyrazole-based carbohydrazone hybrids have been considered to be a remarkable class of compounds in pharmaceutical chemistry. Here, we reported bioactivities of 4-(3-(2-(arylidene)hydrazin-1-carbonyl)-5-phenyl-1H-pyrazol-1-yl)benzenesulfonamides (1–27) towards CA isoenzymes (hCA I, hCA II, hCA IX) and human oral squamous cell carcinoma cell line. Compounds 19 (Ki = 10.1 nM, hCA I/hCA IX = 749.6), 22 (Ki = 18.5 nM, hCA I/hCA IX = 429.2), 26 (Ki = 14.5 nM, hCA I/hCA IX = 596.9), 27 (Ki = 21.5 nM, hCA I/hCA IX = 413.1) were more potent and selective inhibitors of cancer-associated hCA IX isoenzyme. Compounds 22 and 26 were also found to be approximately three times more selective hCA IX inhibitors over off-target hCA II at low nanomolar. Compounds 19, 22, 23, 24, and 26 with IC50 of 1.6–1.7 μM showed potent cytotoxicity against human oral squamous cell carcinoma cell line as compared with human gingival fibroblast, producing the tumor-specificity value over 100. This was due to its cytostatic growth inhibition accompanied by a slight but significant dose-dependent increase in cell shrinkage and subG1 cell accumulation and marginal activation of caspase 3 substrates. Bioassay results showed that carbohydrazone-based hybrids could be useful candidates to design novel anticancer compounds and selective carbonic anhydrase inhibitors.