Background:

Bifonazole (Bay H-4502) is an imidazole antifungal drug.

Bifonazole (Bay H-4502), a new broad-spectrum antimycotic, interferes with sterol biosynthesis. In dermatophytes bifonazole additionally inhibits directly HMG-CoA-reductase. bifonazole possesses a sequential mode of action, namely inhibition of cytochrome P450-dependent C14-demethylation of sterols and direct inhibition of HMG-CoA-reductase. In vitro Bifonazole (Bay H-4502) shows a strongly pH-dependent efficacy. The uptake kinetics of Bifonazole (Bay H-4502) have been measured with different pathogens[1]. Bifonazole (Bay H-4502) additionally leads to a generally decreased rate of sterol biosynthesis as compared to clotrimazole, due to a direct inhibition of microsomal HMG-CoA-reductase. The additional fungicidal effects of Bifonazole (Bay H-4502) are considered to originate from a sequential action by inhibition of HMG-CoA-reductase and of cytochrome P450[2]. Bifonazole (Bay H-4502) were affected by choice of medium with Kimmig's agar generally giving the lowest MIC's. Bifonazole MICs were shown to vary with pH (maximal activity at pH 6.5) with selected yeasts when tested on Kimmig's agar[3].

参考文献:
[1]. Berg, D. and M. Plempel, Bifonazole, a biochemist's view. Dermatologica, 1984. 169 Suppl 1: p. 3-9.
[2]. Berg, D., et al., Bifonazole and clotrimazole. Their mode of action and the possible reason for the fungicidal behaviour of bifonazole. Arzneimittelforschung, 1984. 34(2): p. 139-46.
[3]. Shadomy, S., D.M. Dixon, and R. May, A comparison of bifonazole (BAY H 4502) with clotrimazole in vitro. Sabouraudia, 1982. 20(4): p. 313-23.