Novel amide derivatives of probenecid, a well-known uricosuric agent, were synthesized and evaluated as inhibitors of human carbonic anhydrases (hCAs, EC 4.2.1.1). The transmembrane isoforms (hCA IX and XII) were potently and selectively inhibited by some of them. The proposed chemical modification led to a complete loss of hCA II inhibition (K(i)s > 10,000 nM) and enhanced the inhibitory activity against the tumour-associated hCA XII (compound 4 showed a K-i value of 15.3 nM). The enzyme inhibitory data have also been validated by docking studies of the compounds within the active site of hCA XII
Selective inhibition of human carbonic anhydrases by novel amide derivatives of probenecid: Synthesis, biological evaluation and molecular modelling studies / D'Ascenzio, M; Carradori, S; Secci, Daniela; Vullo, D; Ceruso, M; Akdemir, A; Supuran, Ct. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - STAMPA. - 22:15(2014), pp. 3982-3988. [10.1016/j.bmc.2014.06.003]
Selective inhibition of human carbonic anhydrases by novel amide derivatives of probenecid: Synthesis, biological evaluation and molecular modelling studies
SECCI, DANIELA;
2014
Abstract
Novel amide derivatives of probenecid, a well-known uricosuric agent, were synthesized and evaluated as inhibitors of human carbonic anhydrases (hCAs, EC 4.2.1.1). The transmembrane isoforms (hCA IX and XII) were potently and selectively inhibited by some of them. The proposed chemical modification led to a complete loss of hCA II inhibition (K(i)s > 10,000 nM) and enhanced the inhibitory activity against the tumour-associated hCA XII (compound 4 showed a K-i value of 15.3 nM). The enzyme inhibitory data have also been validated by docking studies of the compounds within the active site of hCA XIII documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
