Current application of arylazoles and annulated azoles in the design of new antileishmanial agents

Leishmaniasis is a group of tropical diseases with high worldwide prevalence and difficulty in management. At present, the development of resistance and the increase of co-infected leishmaniasis with AIDS have become a serious public health problem. Thus, designing and discovery of effective and non-toxic drugs for the treatment of this disease is very urgent. Azole derivatives have displayed a wide range of biological activities. The pharmacological interest of azole compounds has been established to find new antileishmanial agents. The usefulness of some well-known azole antifungals has been also reported previously. Generally, azole antifungals have a common pharmacophoric portion namely N-phenethylazole and act by inhibiting the cytochrome P-450-mediated 14α-demethylation of lanosterol. Apart from azole antifungals with N-phenethylazole structure, a variety of N-aryl azoles and fused azole derivatives have been reported as antileishmanial agents. These compounds possess distinct structure and mechanism of action differing from those of azole antifungals. Thus, in this paper we reviewed the current application of N-aryl azoles and fused azoles for the design and development of new antileishmanial agents.