Martínez-Matías Nelson, Rodríguez-Medina José R
Department of Biochemistry, University of Puerto Rico Medical Sciences Campus, San Juan, PR.
P R Health Sci J. 2018 Sep;37(3):135-142.
Azoles are the most widely used drugs in antifungal therapy. They have a wide spectrum of activity against pathogenic fungi that are clinically relevant. However, they have been associated with adverse reactions and toxicity, both of which can be significant in patients. Compared to diazoles, triazoles discriminate better between their intended molecular target, the fungal CYP51 enzyme, and several enzymes of the human CYP450 system. Over the years, this superior discrimination has led to the favoring of triazoles over diazoles in the treatment of systemic mycoses. Nevertheless, despite their being better able to discriminate between the fungal CYP51 and host CYP450 enzymes, they are still capable of inducing significant toxicity and adverse reactions in the host, especially when taken concomitantly with other therapeutic drugs by patients with compromised immune systems. In this writing, we review some of the fundamental concepts regarding the chemistry and mechanisms of action of azole compounds, as well as the spectrum of activity, pharmacokinetics, and adverse effects of triazole antifungals. In addition, we discuss some of the mechanisms that pathogenic fungi have developed to overcome the cytotoxic effects of therapeutic drugs, with an emphasis on triazoles.
唑类药物是抗真菌治疗中使用最广泛的药物。它们对临床上相关的致病真菌具有广泛的活性。然而，它们与不良反应和毒性有关，这两者在患者中都可能很严重。与二唑类相比，三唑类在其预期的分子靶点真菌CYP51酶和人类CYP450系统的几种酶之间具有更好的区分能力。多年来，这种卓越的区分能力使得在系统性真菌病的治疗中三唑类比二唑类更受青睐。尽管如此，尽管它们能够更好地区分真菌CYP51和宿主CYP450酶，但它们仍然能够在宿主中引起显著的毒性和不良反应，尤其是当免疫系统受损的患者同时服用其他治疗药物时。在本文中，我们回顾了一些关于唑类化合物的化学和作用机制的基本概念，以及三唑类抗真菌药物的活性谱、药代动力学和不良反应。此外，我们讨论了致病真菌为克服治疗药物的细胞毒性作用而发展出的一些机制，重点是三唑类。
