Vanreppelen Giel, Wuyts Jurgen, Van Dijck Patrick, Vandecruys Paul
KU Leuven Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, Kasteelpark Arenberg 31, B-3001 Leuven, Belgium.
J Fungi (Basel). 2023 Jan 28;9(2):171. doi: 10.3390/jof9020171.
Due to their eukaryotic heritage, the differences between a fungal pathogen's molecular makeup and its human host are small. Therefore, the discovery and subsequent development of novel antifungal drugs are extremely challenging. Nevertheless, since the 1940s, researchers have successfully uncovered potent candidates from natural or synthetic sources. Analogs and novel formulations of these drugs enhanced the pharmacological parameters and improved overall drug efficiency. These compounds ultimately became the founding members of novel drug classes and were successfully applied in clinical settings, offering valuable and efficient treatment of mycosis for decades. Currently, only five different antifungal drug classes exist, all characterized by a unique mode of action; these are polyenes, pyrimidine analogs, azoles, allylamines, and echinocandins. The latter, being the latest addition to the antifungal armamentarium, was introduced over two decades ago. As a result of this limited arsenal, antifungal resistance development has exponentially increased and, with it, a growing healthcare crisis. In this review, we discuss the original sources of antifungal compounds, either natural or synthetic. Additionally, we summarize the existing drug classes, potential novel candidates in the clinical pipeline, and emerging non-traditional treatment options.
由于真菌病原体具有真核生物的遗传特性，其分子构成与人类宿主之间的差异很小。因此，新型抗真菌药物的发现及后续研发极具挑战性。尽管如此，自20世纪40年代以来，研究人员已成功从天然或合成来源中发现了有效的候选药物。这些药物的类似物和新型制剂改善了药理学参数，提高了整体药物疗效。这些化合物最终成为新型药物类别的创始成员，并成功应用于临床，数十年来为真菌病提供了有价值且高效的治疗。目前，仅有五种不同类型的抗真菌药物，它们均具有独特的作用方式，分别是多烯类、嘧啶类似物、唑类、烯丙胺类和棘白菌素类。后者是抗真菌药物库中的最新成员，于二十多年前被引入。由于抗真菌药物种类有限，抗真菌耐药性的发展呈指数级增长，随之而来的是日益严重的医疗危机。在本综述中，我们讨论了抗真菌化合物的原始来源，包括天然来源和合成来源。此外，我们总结了现有的药物类别、临床研发中的潜在新型候选药物以及新兴的非传统治疗选择。
