201. 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.
- Author
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Yamali C, Inci Gul H, Ozli G, Angeli A, Ballar Kirmizibayrak P, Erbaykent Tepedelen B, Sakagami H, Bua S, and Supuran CT
- Subjects
- Antigens, Neoplasm metabolism, Apoptosis drug effects, Carbonic Anhydrase IX antagonists & inhibitors, Carbonic Anhydrase IX metabolism, Carbonic Anhydrases metabolism, Cell Line, Tumor, Humans, Neoplasms drug therapy, Neoplasms enzymology, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Carbonic Anhydrase Inhibitors chemistry, Carbonic Anhydrase Inhibitors pharmacology, Pyrazoles chemistry, Pyrazoles pharmacology
- 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., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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