Benzoxaboroles Are Inhibitors of the η-Class Carbonic Anhydrase From Plasmodium falciparum

Malaria remains a major global health burden, compounded by increasing resistance to current therapies. Plasmodium falciparum carbonic anhydrase (PfaCA), a η-class metalloenzyme essential for the parasite metabolism and survival, has recently emerged as a promising antimalarial target. In this study, benzoxaborole 4 and its 6-substituted triazolyl derivatives (5–18) were evaluated for PfaCA inhibition and in vitro antiplasmodial activity against the P. falciparum 3D7 strain. Compounds 13 and 14 emerged as the most potent inhibitors (KI = 0.45 and 0.43 µM, respectively) of the enzyme, coupled with notable antiplasmodial activity (IC50 = 34 and 47 µM). Among the tested compounds, the ethyl ester 7 demonstrated the strongest antiplasmodial activity (IC50 = 2.5 µM). Molecular docking studies further supported the favorable binding of active derivatives within the PfaCA active site. These findings highlight the potential of benzoxaborole-based scaffolds as a new chemotype for antimalarial drug development.