Drug Resistance in Cryptococcus neoformans

Improved potency and reduced toxicity of the antifungal peptoid AEC5 through submonomer modification

“…5–7 Amplifying these side effects is the fact that most current therapeutic regimen include combination or long-term drug treatments due to increasingly observed resistance in many fungal pathogens. 6,8 The dearth of suitable treatments necessitates new therapeutic options for patients dealing with fungal infections.…”

Discovery and Characterization of a Peptoid with Antifungal Activity against Cryptococcus neoformans

“…8−10 Drug resistance has also been observed against these therapeutics in several fungal species and strains. 11 Because of this resistance, current treatments usually include a cocktail or extended regimen of these drugs and possible surgery if there is no response to medication, necessitating new therapeutic options for patients dealing with fungal infections. 9 One alternative to combat high toxicity levels and drug resistance is the use of antimicrobial peptides (AMPs), which can display minimal toxicity to mammalian cells and may be able to specifically target fungal cells.…”

“…Treatment for infections due to organisms such as Aspergillus , Candida , and Cryptococcus vary depending upon the patient and species of the infectious organism. Current therapeutics, such as amphotericin B, flucytosine, and fluconazole, carry their own risks, including high mammalian cytotoxicity that results in gastrointestinal complications, vomiting, QT prolongation, and hepatitis. − Drug resistance has also been observed against these therapeutics in several fungal species and strains . Because of this resistance, current treatments usually include a cocktail or extended regimen of these drugs and possible surgery if there is no response to medication, necessitating new therapeutic options for patients dealing with fungal infections …”

Discovery and Characterization of a Rapidly Fungicidal and Minimally Toxic Peptoid against Cryptococcus neoformans

“…11 The need for novel antifungal agents is magnified by the increasing emergence of fungi with resistance to the limited arsenal of clinical antifungals. 12,13 One promising class of antifungal compounds are peptoids, or Nsubstituted glycines. Peptoids are a proteolytically stable peptidomimetic and can be designed to mimic naturally occurring antimicrobial peptides.…”

“…Unfortunately, these clinical antifungal agents often present severe nephrotic and hepatic toxicities and can induce long-term side effects . The need for novel antifungal agents is magnified by the increasing emergence of fungi with resistance to the limited arsenal of clinical antifungals. , One promising class of antifungal compounds are peptoids, or N-substituted glycines. Peptoids are a proteolytically stable peptidomimetic and can be designed to mimic naturally occurring antimicrobial peptides. − Our group and others have reported the development of peptoids effective against both C. albicans and C. neoformans in vitro. − Many of these compounds are lipopeptoids, containing a long aliphatic tail on the N-terminus to improve antifungal activity of relatively short peptoids.…”