抗真菌感染新药研究进展

Advances in research on new antifungal drugs

随着免疫功能缺陷人群的增多,侵袭性真菌感染(invasive fungal infections,IFIs)的发病率和死亡率逐年上升,严重威胁人类健康。目前临床常用抗侵袭性真菌感染药物有三唑类(氟康唑)、多烯类(两性霉素B)、棘白菌素类(卡泊芬净)等,然而这些药物并不能满足临床需要,侵袭性真菌感染的死亡率仍居高不下。因此,本文着重于目前处于临床研究阶段的抗真菌感染新药,根据作用靶点不同依次介绍:作用于细胞壁的新型葡聚糖合成酶抑制剂CD101和SCY-078、几丁质合成酶抑制剂尼可霉素Z、GPI锚定蛋白抑制剂APX001;作用于细胞膜的CYP51抑制剂VT-1161和VT-1129、破坏细胞膜通透性药物CAmB;影响细胞代谢的嘧啶合成抑制剂F901318,以及生物制剂包括细胞表面凝集素样序列3蛋白疫苗(NDV-3)和抗真菌感染抗体Mycograb。本文主要综述了上述新药的研究进展,包括作用机制、体内外活性、临床研究结果等,为相关药物的研发与未来的临床应用提供参考。

The morbidity and mortality of invasive fungal infections(IFIs)are on the increase in recent several years owing to the growing number of immunodeficient patients,and lead to a serious threat to human health.At present,triazoles(fluconazole),polyenes(amphotericin B)and echinocandins(caspofungin),as routine anti-IFIs drugs,are widely administrated in clinical practice.However,the present therapeutic regime in IFIs remains dismal despite decades of efforts in anti-IFIs drugs.Therefore,evaluating the correlation between frontier antifungal drugs and their effects on clinical phases were warranted.In this review,we present various therapeutic targets,including fungal cell wall,cell membrane,cell metabolism,and biological agents.CD101 and SCY-078 inhibiting glucan synthase,nikkomycins Z inhibiting chitin synthase,APX001 inhibiting GPI-anchored protein,VT-1161 and VT-1129 inhibiting fungal CYP51,CAmB disrupting cell membrane permeability,F901318 inhibiting pyrimidine synthesis,cell surface lectin-like sequence 3 protein vaccine(NDV-3)and antifungal infection antibody mycograb were also fully discussed.Besides,this article reviews the research progress of the anti-IFIs drugs as mentioned above,including the functional mechanism,activities in vitro and vivo,outcomes of clinical research,providing an overview of diverse anti-IFIs in the past decades and an outlook for the development of related drugs.