p-Amino acids - Cyclic p-amino acids have been reported with a dual mode of action where one mechanism is the inhibition of protein synthesis after concentrative uptake and second is interference with self-regulatory mechanisms of amino acid metabolism. 2-Aminocyclohex-3-enecarboxylic acid, (1) designed as a pyridoxal phosphate suicide inhibitor, and cispentacin (2), a natural p-amino acid, were both shown to be active against C. albicans.
PLD-118 (10-8888, 3), obtained during a derivatization program, is a novel orally available p-amino acid which shows an in vitro IC50 of 0.13 mg/mL activity against C. albicans (8). PLD-118 is currently being investigated in Phase II clinical trials. Positive in vivo efficacy of orally administered PLD-118 was reported in mice using lethal systemic infection models for C. albicans or non-lethal kidney infection models for C. glabrata or C. krusei. PLD-118 was also effective against infections caused by fluconazole-resistant strains (9).
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