TY - JOUR
T1 - Carbonic anhydrase inhibitors. Inhibition of the fungal beta-carbonic anhydrases from Candida albicans and Cryptococcus neoformans with boronic acids
AU - Innocenti, Alessio
AU - Winum, Jean-Yves
AU - Hall, Rebecca
AU - Mühlschlegel, Fritz A
AU - Scozzafava, Andrea
AU - Supuran, Claudiu T
PY - 2009/5/15
Y1 - 2009/5/15
N2 - Inhibition of the beta-carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic fungi Cryptococcus neoformans (Can2) and Candida albicans (Nce103) with a series of aromatic, arylalkenyl- and arylalkylboronic acids was investigated. Aromatic, 4-phenylsubstituted- and 2-naphthylboronic acids were the best Can2 inhibitors, with inhibition constants in the range of 8.5-11.5microM, whereas arylalkenyl and aryalkylboronic acids showed K(I)s in the range of 428-3040microM. Nce103 showed a similar inhibition profile, with the 4-phenylsubstituted- and 2-naphthylboronic acids possessing K(I)s in the range of 7.8-42.3microM, whereas the arylalkenyl and aryalkylboronic acids were weaker inhibitors (K(I)s of 412-5210microM). The host human enzymes CA I and II were also effectively inhibited by these boronic acids. The B(OH)(2) moiety is thus a new zinc-binding group for designing effective inhibitors of the alpha- and beta-CAs.
AB - Inhibition of the beta-carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic fungi Cryptococcus neoformans (Can2) and Candida albicans (Nce103) with a series of aromatic, arylalkenyl- and arylalkylboronic acids was investigated. Aromatic, 4-phenylsubstituted- and 2-naphthylboronic acids were the best Can2 inhibitors, with inhibition constants in the range of 8.5-11.5microM, whereas arylalkenyl and aryalkylboronic acids showed K(I)s in the range of 428-3040microM. Nce103 showed a similar inhibition profile, with the 4-phenylsubstituted- and 2-naphthylboronic acids possessing K(I)s in the range of 7.8-42.3microM, whereas the arylalkenyl and aryalkylboronic acids were weaker inhibitors (K(I)s of 412-5210microM). The host human enzymes CA I and II were also effectively inhibited by these boronic acids. The B(OH)(2) moiety is thus a new zinc-binding group for designing effective inhibitors of the alpha- and beta-CAs.
KW - Boronic Acids
KW - Candida albicans
KW - Carbonic Anhydrase Inhibitors
KW - Carbonic Anhydrases
KW - Cryptococcus neoformans
KW - Humans
KW - Structure-Activity Relationship
U2 - 10.1016/j.bmcl.2009.03.147
DO - 10.1016/j.bmcl.2009.03.147
M3 - Article
C2 - 19375309
SN - 0960-894X
VL - 19
SP - 2642
EP - 2645
JO - Bioorganic & Medicinal Chemistry Letters
JF - Bioorganic & Medicinal Chemistry Letters
IS - 10
ER -