Allylamine Antifungal Drugs

Parasitological cure of Chagas disease: is it possible? Is it relevant?

“…Sterol biosynthesis inhibitors (SBI) have been found to be particularly useful, as endogenous sterols are essential for survival in these pathogenic organisms; these compounds are in most cases orally active, have broad spectrum of activity and very low toxicity (Ryder & Mieth 1992, Mercer 1993, Vanden Bossche 1995. T. cruzi has also an absolute requirement of specific endogenous sterols for cell viability and proliferation and is extremely sensitive to sterol biosynthesis inhibitors (SBI) in vitro (Docampo et al 1981, Beach et al 1986, Goad et al 1989, Urbina et al 1988, 1993, 1996b; thus, the sterol biosynthesis pathway in this organism is a valid chemotherapeutic target (Urbina 1997).…”

Effects of naftifine and terbinafine, two allylamine antifungal drugs, on selected functions of human polymorphonuclear leukocytes

“…We did not evaluate whether terbinafine's effect on yeast survival was due to the adherence of C. albicans to the PMNs, phagocytosis of C. albicans, or the killing of C. albicans following phagocytosis. DISCUSSION Therapeutic concentrations of terbinafine are about 0.8 to 1.5 ,ug/ml in blood (3 ,uM) and are up to 9 ,ug/g of tissue in the stratum corneum (44). Naftifine is not absorbed by the oral route and is only intended for topical application.…”

“…This class of drugs contains many different chemical entities with specific mechanisms of antifungal action (25,40,44,46,48). Antifungal drugs may also have immunosuppressive effects, acting on the host's natural or specific immunity (7,16,24,26,55).…”

“…The ability of amphotericin B to increase the activities of PMNs and macrophages may be the reason for its inflammatory properties (52,53). The allylamines (naftifine and terbinafine), a new generation of broad-spectrum antimycotic compounds, have recently been developed; they act by interfering with squalene 2,3-epoxidase, which results in decreased amounts of the principal membrane sterols, especially ergosterol (44,48). Naftifine, a topically administered allylamine, has been shown to inhibit PMN function; specifically, naftifine was shown to depress chemotaxis, chemokinesis, chemiluminescence, and superoxide anion production (51).…”

“…However, depressant effects were observed at relatively high concentrations (about 30 ,ug/ml), which were associated with a certain amount of selective cytotoxicity against PMNs (51). Terbinafine is an orally effective allylamine derivative (44) (13). The PMNs were washed and resuspended in Hanks balanced salt solution (HBSS) at a concentration of 107 cells per ml and were kept in ice-cold buffer until they were used.…”