Synthesis of coumarin-sulfonamide derivatives and determination of their cytotoxicity, carbonic anhydrase inhibitory and molecular docking studies.

Synthesis of coumarin-sulfonamide derivatives and determination of their cytotoxicity, carbonic anhydrase inhibitory and molecular docking studies. Eur J Med Chem. 2019 Sep 14;183:111702 Authors: Zengin Kurt B, Sonmez F, Ozturk D, Akdemir A, Angeli A, Supuran CT Abstract Carbonic anhydrases isoforms CA IX, and XII are known to be highly expressed in various human tissues and malignancies. CA IX is a prominent target for especially colorectal cancers, because it is overexpressed in colorectal cancer and this overexpression leads poor prognosis. Inhibition of CA IX activity by small molecule CA inhibitors like sulfonamides, sulfonamide derivative or coumarins leads to inhibition of tumorigenesis. Novel twenty-seven compounds in three series (sulfonamide-based imines (6a-6i), coumarin-based aldehydes (7a-7i), and coumarin-sulfonamide-based target molecules (8a-8i)) were synthesized and characterized by means of IR, NMR, and mass spectra. All compounds were tested for their ability to inhibit CA I, CA II, CA IX, and CA XII isoforms. 4-((((2-((1-(3-((2-oxo-2H-chromen-7-yl)oxy)propyl)-1H-1,2,3-triazol-4-yl)methoxy)naphthalen-1-yl)-methylene)amino)methyl)benzenesulfonamide (8i) exhibited the highest hCA IX inhibition with the Ki of 45.5 nM. In addition, 8i was found to be potent in inhibiting cancer cell proliferation as selective (IC50 = 17.01 ± 1.35 μM for HT-29, IC50 = 118.73 ± 1.19 μM for HEK293T). This novel c...
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Tags: Eur J Med Chem Source Type: research