Guanidine-Containing Antifungal Agents against Human-Relevant Fungal Pathogens (2004–2022)—A Review

Abstract

The guanidine moiety is typically a highly basic group, and can be found in a wide variety of drugs, such as zanamivir (Relenza) and metformin (Fortamet), as well as in biologically active compounds for numerous disease areas, including central nervous system (CNS) diseases and chemotherapeutics. This review will focus on antifungal agents which contain at least one guanidine group, for the treatment of human-related fungal pathogens, described in the literature between 2004 and 2022. These compounds include small molecules, steroids, polymers, metal complexes, sesquiterpenes, natural products, and polypeptides. It shall be made clear that a diverse range of guanidine-containing derivatives have been published in the literature and have antifungal activity, including efficacy in in vivo experiments.

Recent developments in membrane targeting antifungal agents to mitigate antifungal resistance

“…189,190 Guanidine is an important pharmacophoric feature that displays potent antimicrobial properties, and Baugh summarized recently reported guanidine-containing antifungal molecules. 191 Oule and co-workers reported polyhexamethylene guanidine (PHMG) hydrochloride as a potent antimicrobial macromolecule that showed broadspectrum antibacterial properties against drug-resistant pathogens with minimal toxicity against mammalian cells. 192 In addition, its physiochemical properties, like water solubility, and non-corrosive and odorless nature, make it a versatile antibacterial disinfectant.…”

Study of the Conformation of Bromated Guanidines with Potential Anti-leishmania Activity

“…Guanidine compounds are often found in nature and used in the synthesis of a variety of organic compounds, such as quinazolines, oxazolidinones, lactones, and carbonates [7][8][9][10][11]. Novel guanidine derivatives exhibit several biological effects, such as cardiovascular dilation, antihistamine properties, anti-inflammatory activity, antidiabetic effects, antibacterial, antifungal, 2 antiprotozoal/antiparasitic properties, and antiviral activity [7,[12][13][14][15][16][17][18][19][20][21]. Recently, some guanidine compounds have been studied in relation to leishmaniasis [22,23].…”

Amide- and bis-amide-linked highly potent and broadly active antifungal agents for the treatment of invasive fungal infections- towards the discovery of pre-clinical development candidate FC12406

“…These compounds were significantly more potent against multiple fungal pathogens than other guanidine-containing antifungal agents including bis-guanidine pyrrole derivatives [ 17 ], bis-guanidine peptidomimetics of lactoferrin [ 20 ], macrocyclic analogs of guazatine [ 21 , 22 ], the arylguanidine abafungin [ 23 ] and mono-aminoguanidine analogs described by Miyazaki et al [ 24 ]. More generally, a wide range of guanidine-containing agents have been described as having antifungal [ 25 ] and antimicrobial [ 26 ] effects, indicative of the potential of guanidine-containing derivatives to serve as potential drugs.

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