Exploring of tumor-associated carbonic anhydrase isoenzyme IX and XII inhibitory effects and cytotoxicities of the novel N-aryl-1-(4-sulfamoylphenyl)-5-(thiophen-2-yl)-1H-pyrazole-3-carboxamides


YAMALI C., GÜL H. İ. , ÖZLİ G., Angeli A., KARA KADAYIFCILAR P., ERBAYKENT TEPEDELEN B., ...More

BIOORGANIC CHEMISTRY, vol.115, 2021 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 115
  • Publication Date: 2021
  • Doi Number: 10.1016/j.bioorg.2021.105194
  • Journal Name: BIOORGANIC CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded, Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Keywords: Carbonic anhydrase, Anticancer, Pyrazole, Benzenesulfonamide, Carboxamide, Apoptosis, cell cycle, ANTIPROLIFERATIVE ACTIVITY, HCA IX, BIOACTIVITIES, CHALCONES, APOPTOSIS

Abstract

A series of novel N-aryl-1-(4-sulfamoylphenyl)-5-(thiophen-2-yl)-1H-pyrazole-3-carboxamides was synthesized and examined as inhibitors of cytosolic (human) hCA I and hCA II, and cancer-related transmembrane hCA IX and hCA XII isoenzymes. AC2 was the most selective inhibitor towards cancer-related hCA IX while AC8 and AC9 selectively inhibited hCA XII over off-target isoenzymes. Anticancer effects of the compounds were evaluated towards human oral squamous cell carcinoma (OSCC) cell lines, human mesenchymal normal oral cells, breast (MCF7), prostate (PC3), non-small cell lung carcinoma cells (A549), and non-tumoral fetal lung fibroblast cells (MRC5). Compounds moderately showed cytotoxicity towards cancer cell lines. Among others, AC6 showed cell specific cytotoxic activity and induced apoptosis in a dose-dependent manner without a significant change in the cell cycle distribution of MCF7. These results suggest that pyrazole-3-carboxamides need further molecular modification to increase their anticancer drug candidate potency.