Exploring of tumor-associated carbonic anhydrase isoenzyme IX and XII inhibitory effects and cytotoxicities of the novel <i>N</i>-aryl-1-(4-sulfamoylphenyl)-5-(thiophen-2-yl)-1<i>H</i>-pyrazole-3-carboxamides
Yamali, Cem, Gul, Halise Inci, Ozli, Gulsen, Angeli, Andrea, Kirmizibayrak, Petek Ballar, Tepedelen, Burcu Erbaykent, Sakagami, Hiroshi, Bua, Silvia, Supuran, Claudiu T.
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.
- Journal
- BIOORGANIC CHEMISTRY
- Year
- 2021
- Volume
- 115
- ISSN
- 0045-2068
- eISSN
- 1090-2120
- DOI
- 10.1016/j.bioorg.2021.105194
- WoS UID
- WOS:000705513300004