Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. They represent a typical example of enzyme convergent evolution, as six genetically unrelated families of such enzymes were described so far. The need to find selective CA inhibitors (CAIs) triggered the investigation of natural product libraries, which proved to be a valid source of agents with such an activity, as demonstrated for the phenols, polyamines and coumarins. Herein we report an in vitro inhibition study of human (h) CA isoforms hCAs I, II, IV, VII and XII with a panel of natural polyphenols including flavones, flavonols, flavanones, flavanols, isoflavones and depsides, some of which extracted from Quercus ilex and Salvia miltiorrhiza. Several of the investigated derivatives showed interesting inhibition activity and selectivities for inhibiting some important isoforms over the off-target ones hCA I and II.
New natural product carbonic anhydrase inhibitors incorporating phenol moieties / Karioti, Anastasia; Ceruso, Mariangela; Carta, Fabrizio; Bilia, Anna-Rita; Supuran, Claudiu T. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - STAMPA. - 23:(2015), pp. 7219-25-7225. [10.1016/j.bmc.2015.10.018]
New natural product carbonic anhydrase inhibitors incorporating phenol moieties
KARIOTI, ANASTASIA;CERUSO, MARIANGELA;CARTA, FABRIZIO;BILIA, ANNA RITA;SUPURAN, CLAUDIU TRANDAFIR
2015
Abstract
Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. They represent a typical example of enzyme convergent evolution, as six genetically unrelated families of such enzymes were described so far. The need to find selective CA inhibitors (CAIs) triggered the investigation of natural product libraries, which proved to be a valid source of agents with such an activity, as demonstrated for the phenols, polyamines and coumarins. Herein we report an in vitro inhibition study of human (h) CA isoforms hCAs I, II, IV, VII and XII with a panel of natural polyphenols including flavones, flavonols, flavanones, flavanols, isoflavones and depsides, some of which extracted from Quercus ilex and Salvia miltiorrhiza. Several of the investigated derivatives showed interesting inhibition activity and selectivities for inhibiting some important isoforms over the off-target ones hCA I and II.I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.