Seleno Containing Compounds as Potent and Selective Antifungal Agents

Abstract

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 f urf ur 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.

Synthesis, Structures and Antifungal Activity of Selenoglycolurils

“…Similarly, the emergence of antifungal resistance highlights the need for new and improved antifungal agents, particularly against drug‐resistant Candida glabrata and Candida auris [2,3] . In this context, the unique properties of organoselenium compounds which efficiently scavenge and induce reactive oxygen species has led to a renewed interest in their application across medicinal chemistry, including use as antifungals and antibacterials [4–10] …”

“…[2,3] In this context, the unique properties of organoselenium compounds which efficiently scavenge and induce reactive oxygen species has led to a renewed interest in their application across medicinal chemistry, including use as antifungals and antibacterials. [4][5][6][7][8][9][10] The chemistry of imidazo [4,5-d]imidazol-2,5(1H,3H)-diones (glycolurils) and their analogs is our area of interest. [11][12][13] We are developing methods for the synthesis of glycolurils I, [11,12] their 5-thioxo II, [11,12] 5-imino III [12] derivatives and 3thioxoperhydroimidazo[4,5-e]-1,2,4-triazin-2-ones IV (3-thioxoimidazotriazin-2-ones) [11] and studying their properties (Figure 1).…”

Benzenesulfonamides Incorporating Hydantoin Moieties Effectively Inhibit Eukaryoticand Human Carbonic Anhydrases

“…The newly developed compounds were also tested for the inhibition of two β-CAs from fungal pathogens. Indeed, in many pathogenic bacteria [41][42][43][44][45][46][47] and fungi [48][49][50][51][52], CAs belonging to several genetic familieshaverelevant physiologic functions and their inhibition may lead to anti-infective effects [53][54][55][56][57].…”