Quinoline-sulfamoyl carbamates/sulfamide derivatives: Synthesis, cytotoxicity, carbonic anhydrase activity, and molecular modelling studies.

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).

• Authors: Elmas Begum Cakmak, Belma Zengin Kurt, Dilek Ozturk Civelek, Andrea Angeli, Atilla Akdemir, Fatih Sonmez, Claudiu T Supuran, Mustafa Kucukislamoglu
• Journal: Bioorganic chemistry (Bioorg Chem) Vol. 110 Pg. 104778 (05 2021) ISSN: 1090-2120 [Electronic] United States
• PMID: 33684713 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Antioxidants
• Carbamates
• Carbonic Anhydrase Inhibitors
• Quinolines
• Sulfonamides
• Sulfonic Acids
• sulfamic acid
• quinoline
• Carbonic Anhydrases

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Antioxidants (chemical synthesis, chemistry, pharmacology)
• Carbamates (chemistry, pharmacology)
• Carbonic Anhydrase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Carbonic Anhydrases (metabolism)
• Cell Line
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Humans
• Models, Molecular
• Molecular Structure
• Quinolines (chemistry, pharmacology)
• Structure-Activity Relationship
• Sulfonamides (chemistry, pharmacology)
• Sulfonic Acids (chemistry, pharmacology)