Carbonic anhydrase (CA) IX, and XII isoforms are known to be highly expressed in various human tissues and malignancies. CA IX is a prominent target for some cancers because it is overexpressed in hypoxic tumors and this overexpression leads to poor prognosis. Novel twenty-seven compounds in two series (sulfamoylcarbamate-based quinoline (2a-2o) and sulfamide-based quinoline (3a-3l)) were synthesized and characterized by means of IR, NMR, and mass spectra. Their inhibitory activities were evaluated against CA I, CA II, CA IX, and CA XII isoforms. 2-Phenylpropyl (N-(quinolin-8-yl)sulfamoyl)carbamate (2m) exhibited the highest hCA IX inhibition with the Ki of 0.5 µM. In addition, cytotoxic effects of the synthesized compounds on human colorectal adenocarcinoma (HT-29; HTB-38), human breast adenocarcinoma (MCF7; HTB-22), human prostate adenocarcinoma (PC3; CRL-1435) and human healthy skin fibroblast (CCD-986Sk; CRL-1947) cell lines were examined. The cytotoxicity results showed that 2j, 3a, 3e, 3f are most active compounds in all cell lines (HT-29, MCF7, PC3, and CCD-986Sk).
Quinoline-sulfamoyl carbamates/sulfamide derivatives: Synthesis, cytotoxicity, carbonic anhydrase activity, and molecular modelling studies / Cakmak E.B.; Zengin Kurt B.; Ozturk Civelek D.; Angeli A.; Akdemir A.; Sonmez F.; Supuran C.T.; Kucukislamoglu M.. - In: BIOORGANIC CHEMISTRY. - ISSN 0045-2068. - ELETTRONICO. - 110:(2021), pp. 104778.104778-104778.104778. [10.1016/j.bioorg.2021.104778]
Quinoline-sulfamoyl carbamates/sulfamide derivatives: Synthesis, cytotoxicity, carbonic anhydrase activity, and molecular modelling studies
Angeli A.;Supuran C. T.;
2021
Abstract
Carbonic anhydrase (CA) IX, and XII isoforms are known to be highly expressed in various human tissues and malignancies. CA IX is a prominent target for some cancers because it is overexpressed in hypoxic tumors and this overexpression leads to poor prognosis. Novel twenty-seven compounds in two series (sulfamoylcarbamate-based quinoline (2a-2o) and sulfamide-based quinoline (3a-3l)) were synthesized and characterized by means of IR, NMR, and mass spectra. Their inhibitory activities were evaluated against CA I, CA II, CA IX, and CA XII isoforms. 2-Phenylpropyl (N-(quinolin-8-yl)sulfamoyl)carbamate (2m) exhibited the highest hCA IX inhibition with the Ki of 0.5 µM. In addition, cytotoxic effects of the synthesized compounds on human colorectal adenocarcinoma (HT-29; HTB-38), human breast adenocarcinoma (MCF7; HTB-22), human prostate adenocarcinoma (PC3; CRL-1435) and human healthy skin fibroblast (CCD-986Sk; CRL-1947) cell lines were examined. The cytotoxicity results showed that 2j, 3a, 3e, 3f are most active compounds in all cell lines (HT-29, MCF7, PC3, and CCD-986Sk).
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