Allylamines
Fungal infections (mycoses) are found throughout the world. Only a few structural classes of compounds currently satisfy the demands of modern chemotherapy in their treatment - Anton Stütz
image by: Aspergillus and Aspergillosis
HWN Suggests
Pharmacology of the allylamines
The allylamines are a new class of antifungal drugs that inhibit ergosterol synthesis at the level of squalene epoxidase. These agents are highly selective for the fungal enzyme and have a minimal effect on mammalian cholesterol synthesis. Naftifine, the original member of the allylamine series, possesses only topical activity, whereas the naftifine analog terbinafine is active both topically and orally. In vitro, terbinafine is exceptionally active against dermatophytes, molds, and dimorphic fungi in which it exerts a fungicidal action. This in vitro profile is reflected by the clinical effectiveness of this allylamine in the treatment of dermatophyte infections. When given orally, terbinafine…
Articles of Interest
Allylamine Derivatives: New Class of Synthetic Antifungal Agents Inhibiting Fungal Squalene Epoxidase
A new class of synthetic antifungal agents, the allylamines, has been developed by modification of naftifine, a topical antimycotic. SF 86-327, the most effective of these compounds so far, is highly active in vitro against a wide range of fungi and exceeds clinical standards in the oral and topical treatment of guinea pig dermatophytoses. SF 86-327 is a powerful specific inhibitor of fungal squalene epoxidase, a key enzyme in sterol biosynthesis.
Allylamine Derivatives—a New Class of Active Substances in Antifungal Chemotherapy
Fungal infections (mycoses) are found throughout the world. Only a few structural classes of compounds currently satisfy the demands of modern chemotherapy in their treatment; hence, the quest for new types of active substances is of major scientific and therapeutic importance. The first representative of a new class of substances–the allylamine derivatives–namely naftifine ((E)-N-methyl-N-(1-naphthylmethyl)-3-phenylallylamine) was discovered by accident and has recently become commercially available as a topical antimycotic.
Allylamines, Benzylamines, and Fungal Cell Permeability: A Review of Mechanistic Effects and Usefulness against Fungal Pathogens
Allylamines, naftifine and terbinafine, and the benzylamine, butenafine, are antifungal agents with activity on the fungal cell membrane. These synthetic compounds specifically inhibit squalene epoxidase, a key enzyme in fungal sterol biosynthesis. This results in a deficiency in ergosterol, a major fungal membrane sterol that regulates membrane fluidity, biogenesis, and functions, and whose damage results in increased membrane permeability and leakage of cellular components, ultimately leading to fungal cell death.
Squalene epoxidase as the target of antifungal allylamines
The allylamine clinical antifungals naftifine and terbinafine inhibit ergosterol biosynthesis at the point of squalene epoxidation in a range of fungi pathogenic to man. Filamentous growth is particularly susceptible to this inhibition, cell death occurring at drug concentrations causing only partial inhibition of ergosterol biosynthesis. Susceptibility of yeast-like fungi such as Candida species is more variable. Squalene epoxidase, a membrane-bound enzyme, is the primary target of the allylamines.
Resources
Allylamines Antifungal Drug
The allylamines (naftifine hydrochloride and terbinafine hydrochloride) are reversible noncompetitive inhibitors of the fungal enzyme squalene monooxygenase (squa-lene 2,3-epoxidase), which coverts squalene to lanos-terol. With a decrease in lanosterol production, ergos-terol production is also diminished, affecting fungal cell membrane synthesis and function. These agents gener-ally exhibit fungicidal activity against dermatophytes and fungistatic activity against yeasts.
