A new series of taurultambenzenesulfonamides 1-17 were prepared and considered for their inhibitory activity in vitro against the Carbonic Anhydrases from Vibrio cholerae (VchCA-?, VchCA-? and VchCA-?) and Burkholderia pseudomallei (BpsCA-? and BpsCA-?). Among the compounds tested, derivatives 4, 5, 7, 10, 12, and 16 resulted in highly effective VchCA? inhibitors (K values spanning within the 6.1-9.6 nM range) and endowed with excellent Selectivity Indexes (SIs; K VchCA-?/K hCA II) all comprised between 0.04 and 0.09. Potent in vitro inhibitors for the BpsCA-? were also identified (Ks of 18.9-19.5 nM). The results here reported may represent the blueprint for the future development of a new generation of CA-based antibiotics integrated with free of resistance mechanisms of action adopted from known drugs.
Taurultams incorporating arylsulfonamide: First in vitro inhibition studies of ?-, ?- and ?-class Carbonic Anhydrases from Vibrio cholerae and Burkholderia pseudomallei
Capasso C;
2021
Abstract
A new series of taurultambenzenesulfonamides 1-17 were prepared and considered for their inhibitory activity in vitro against the Carbonic Anhydrases from Vibrio cholerae (VchCA-?, VchCA-? and VchCA-?) and Burkholderia pseudomallei (BpsCA-? and BpsCA-?). Among the compounds tested, derivatives 4, 5, 7, 10, 12, and 16 resulted in highly effective VchCA? inhibitors (K values spanning within the 6.1-9.6 nM range) and endowed with excellent Selectivity Indexes (SIs; K VchCA-?/K hCA II) all comprised between 0.04 and 0.09. Potent in vitro inhibitors for the BpsCA-? were also identified (Ks of 18.9-19.5 nM). The results here reported may represent the blueprint for the future development of a new generation of CA-based antibiotics integrated with free of resistance mechanisms of action adopted from known drugs.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
