Azoles, enzyme-inhibiting effects

This is not discussed in detail since mechanisms of resistance have been carefully reviewed (Ghannoum and Rice 1999). It was pointed out that resistance has not been associated with modification of the structure. For the 1,2,4-triazoles that have been widely used, their effect is due to inhibition of the synthesis of ergosterol that is the dominant component of fungal cell membranes. Resistance is generally associated with modification of the target enzymes, for example, the epoxidation of squalene (Terbinafine) or 14a-demethylase (Fluconazole). Resistance of Candida albicans to the azole antifungal agent fluconazole demonstrated, however, the simultaneous occurrence of several types of mechanism for resistance (Perea et al. 2001) ... 

Keto con azole Inhibits several 200 mg twice reactions develops with continued use. Hematologic disturbances and hypothyroidism also seen. Generally well High potential for drug interactions due to potent induction of hepatic enzymes. Effective in a majority of causes ... 

Paclobutrazol is a triazole plant growth retardant which also has fungicidal properties [1]. It is an inhibitor of cytochrome P-450 dependant enzymes such as ent-kaurene oxidase and sterol 14a-methyl-demethylase [1]. The fungicidal activity of azole compounds is believed to result from the inhibition of sterol 14a-demethylation. This causes an accumulation of 14a-methylsterols and loss of ergosterol which may have adverse effects on membrane properties [2]. However, there is evidence for other essential requirements for sterol In cell proliferation in addition to a membrane structural role [3-6].For example, in yeast mutants traces of ergosterol stimulate phospholipid formation [7] and protein kinase activity [8]. This report describes the effects of paclobutrazol on the sterol and phospholipid compositions of membranes from plant and yeast cultures. 

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