Synthesis, computational studies and assessment of in vitro inhibitory activity of umbelliferon-based compounds against tumour-associated carbonic anhydrase isoforms IX and XII
Coumarins are widely diffused secondary metabolites possessing a plethora of biological activities. It has been established that coumarins represent a peculiar class of human carbonic anhydrase (hCA) inhibitors having a distinct mechanism of action involving a non-classical binding with amino acid r...
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| Main Authors: | , , , , , , |
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| Format: | Book |
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Taylor & Francis Group,
2020-01-01T00:00:00Z.
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| Online Access: | Connect to this object online. |
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| Summary: | Coumarins are widely diffused secondary metabolites possessing a plethora of biological activities. It has been established that coumarins represent a peculiar class of human carbonic anhydrase (hCA) inhibitors having a distinct mechanism of action involving a non-classical binding with amino acid residues paving the entrance of hCA catalytic site. Herein, we report the synthesis of a small series of new coumarin derivatives 7-11, 15, 17 prepared via classical Pechmann condensation starting from resorcinol derivatives and suitable β-ketoesters. The evaluation of inhibitory activity revealed that these compounds possessed nanomolar affinity and high selectivity towards tumour-associated hCA IX and XII over cytosolic hCA I and hCA II isoforms. To investigate the binding mode of these new coumarin-inspired inhibitors, the most active compounds 10 and 17 were docked within hCA XII catalytic cleft. |
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| Item Description: | 1475-6366 1475-6374 10.1080/14756366.2020.1786821 |