Seleno Containing Compounds as Potent and Selective Antifungal Agents

• DOI: 10.1021/acsinfecdis.2c00250
• Publication Date: 2022-08-19T14:48:20Z
• Authors: Andrea Angeli; Alice Velluzzi; Silvia Selleri; Clemente Capasso; Costanza Spadini; Mattia Iannarelli; Clotilde S. Cabassi; Fabrizio Carta; Claudiu T. Supuran
• Keywords: 0301 basic medicine; 570; Antifungal Agents; 610; Selenourea; Antifungal; Sulfonamide; Selenoureas; Carbonic Anhydrase; 03 medical and health sciences; Antifungal Agent; Animals; Humans; Candida; Carbonic Anhydrases; Antifungals; Sulfonamides; Malassezia; Sheep; Animal; Fungi; Antifungals; Candida; Carbonic Anhydrases; Fungi; Malassezia; Selenoureas; Animals; Antifungal Agents; Cattle; Humans; Sheep; Sulfonamides; Carbonic Anhydrases; Mycoses; Candid; 3. Good health; Mycoses; Cattle; Human

Fungal promoted infections are becoming a severe health global emergency due to drug-resistant phenomena and zoonosis. This work investigated compounds bearing acyl-/selenoureido moieties and primary/secondary sulfonamide groups as novel antifungal agents acting through organism-directed selenium toxicity and inhibition of the newly emergent therapeutic target, the Carbonic Anhydrases (CAs; EC 4.2.1.1). Reported data clearly indicate that seleno-containing scaffolds with respect to the standard-of-care drugs showed appreciable antifungal activity, which was suppressed when the chalcogen was replaced with its cognate isosteric elements sulfur and oxygen. In addition, such compounds showed excellent selectivity against Malassezia pachydermatis over its related genus strains Malassezia furfur and Malassezia globosa. Safe cytotoxicity profiles on bovine kidney cells (MDBK) and human HaCat cells, as well as the shallow hemolytic activity on defibrinated sheep blood, allowed us to consider these compounds as up-and-coming novel antifungals.