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
Makaleler > Tam Makale · 2021
Yazarlar: CEM YAMALI, Halise İnci GÜL, GÜLSEN ÖZLİ, Andrea Angeli, Petek BALLAR KIRMIZIBAYRAK, BURCU ERBAYKENT TEPEDELEN, Hiroshi Sakagami, Silvia Bua, Claudiu T. Supuran
Bioorganic Chemistry, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2021, cilt 115, ss 105194-105194
DOI: 10.1016/j.bioorg.2021.105194
Özet
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.