Novel antifungal β-amino acids: synthesis and activity against Candida albicans

Natural products as lead compounds in drug discovery

“…Amphotericin B is commonly used to treat fungal infections but is known to have significant toxicity, leading to mild clinical responses including chills, fever, headache, nausea and vomiting, and (more seriously) dose-limiting nephrotoxicity [203]. A number of other antifungal agents are in clinical development, including SPK-843 99, in phase III trials for treatment of systemic mycosis [204] and PLD-118 (Icofungipen) 100, a NP-derived synthetic compound in phase II clinical trials [205].…”

Mild and efficient ring opening of monoterpene-fused β-lactam enantiomers. Synthesis of novel β-amino acid derivatives

“…[21][22][23][24] Besides their diverse chemical compositions, β-amino acids and their derivatives possess noteworthy pharmacological effects; for example, (1R,2S)-2-aminocyclopentanecarboxylic acid (cispentacin) and some other alicyclic β-amino acids have marked antifungal activity. 25 The present work describes a mild and efficient ring opening of monoterpene-fused β-lactam enantiomers derived from (+)-and (-)-α-pinene, to produce a novel chiral β-amino acid and its derivatives.…”

Efficacy of PLD-118, a Novel Inhibitor of Candida Isoleucyl-tRNA Synthetase, against Experimental Oropharyngeal and Esophageal Candidiasis Caused by Fluconazole-Resistant C. albicans

“…1). The mechanism of action of PLD-118 is thought to arise from the inhibition of isoleucyltRNA synthetase, resulting in the inhibition of protein synthesis and of fungal cell growth (16,32,33). In vitro studies have Little is known, however, about the activity of PLD-118 against OPEC in immunocompromised hosts.…”