Taurultams incorporating arylsulfonamide: First in vitro inhibition studies of α-, β- and γ-class Carbonic Anhydrases from Vibrio cholerae and Burkholderia pseudomallei

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-α, VchCA-β and VchCA-γ) and Burkholderia pseudomallei (BpsCA-β and BpsCA-γ). Among the compounds tested, derivatives 4, 5, 7, 10, 12, and 16 resulted in highly effective VchCAα inhibitors (K_I values spanning within the 6.1-9.6 nM range) and endowed with excellent Selectivity Indexes (SIs; K_I VchCA-α/K_I hCA II) all comprised between 0.04 and 0.09. Potent in vitro inhibitors for the BpsCA-γ were also identified (K_Is 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.