Anticancer effects of new dibenzenesulfonamides by inducing apoptosis and autophagy pathways and their carbonic anhydrase inhibitory effects on hCA I, hCA II, hCA IX, hCA XII isoenzymes

Gül H. İ., Yamali C., Bulbuller M., Kirmizibayrak P. B., Gül M., Angeli A., ...Daha Fazla

BIOORGANIC CHEMISTRY, cilt.78, ss.290-297, 2018 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 78
  • Basım Tarihi: 2018
  • Doi Numarası: 10.1016/j.bioorg.2018.03.027
  • Dergi Adı: BIOORGANIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.290-297
  • Anahtar Kelimeler: Sulfonamide, Pyrazole, Carbonic anhydrase, Anticancer, Apoptosis, Autophagy, PYRAZOLE DERIVATIVES, CRYSTAL-STRUCTURE, PHASE-I, ANTITUMOR, SULFONAMIDES, BIOACTIVITIES, CYTOTOXICITY, DISCOVERY, CLEAVAGE, DESIGN
  • Çukurova Üniversitesi Adresli: Hayır

Özet

In this study, new dibenzensulfonamides, 7-9, having the chemical structure 4,4'-(5'-chloro-3'-methyl-5aryl-3,4-dihydro-1'H, H-[3,4'-bipyrazole]-1',2-diyl) dibenzenesulfonamide were synthesized in five steps to develop new anticancer drug candidates. Their chemical structures were confirmed by H-1 NMR, C-13 NMR and HRMS spectra. Cytotoxicities of the dibenzensulfonamides were investigated towards HCC1937, MCF7, HeLa, A549 as tumor cell lines and towards MRC5 and Vero as non-tumor cells. Carbonic anhydrase (CAs, EC 4.2.1.1) inhibitory effects of the dibenzensulfonamides 7-9 were also evaluated on the cytosolic human (h) hCA I and II and the tumor-associated hCA IX and XII isoenzymes. Results indicate that both 7 and 8 induced cleavage of poly (ADP ribose) polymerase (PARP), activation of caspases -3, -7 and -9 which are the hallmarks of apoptosis. Meanwhile both compounds induced autophagy in HCC1937 cells which is shown by enhanced expression of LC3 and decreased level of p62 protein. The compounds tested were also effectively inhibited tumor-associated hCA IX and hCA XII isoenzymes in the range of 20.7-28.1 nM and 4.5-9.3 nM, respectively. (C) 2018 Elsevier Inc. All rights reserved.