Taurultams incorporating arylsulfonamide: First in vitro inhibition studies of α-, β- and γ-class Carbonic Anhydrases from Vibrio cholerae and Burkholderia pseudomallei
Makaleler > Tam Makale · 2021
Yazarlar: Özlem AKGÜL, Andrea Angeli, Silvia Selleri, Clemente Capasso, Claudiu T. Supuran, Fabrizio Carta
European Journal of Medicinal Chemistry, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2021, cilt 219, ss 113444-113444
DOI: 10.1016/j.ejmech.2021.113444
Özet
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-alpha, VchCA-beta and VchCA-gamma) and Burkholderia pseudomallei (BpsCA-beta and BpsCA-gamma). Among the compounds tested, derivatives 4, 5, 7, 10, 12, and 16 resulted in highly effective VchCA alpha inhibitors (K-I values spanning within the 6.1-9.6 nM range) and endowed with excellent Selectivity Indexes (SIs; K-I VchCA-alpha/K-I hCA II) all comprised between 0.04 and 0.09. Potent in vitro inhibitors for the BpsCA-gamma were also identified (K(I)s 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. (C) 2021 Elsevier Masson SAS. All rights reserved.