具有协同抗耐药真菌活性的天然小分子化合物研究进展

Research progress of the natural small molecular products synergistically with antifungal agents to inhibit drug-resistant fungi

近几十年来,一方面深部真菌感染发生率呈显著上升趋势,另一方面真菌耐药性包括天然耐药和获得性耐药成为侵袭性真菌感染治疗失败的主要原因之一。现有抗真菌药物品种数量有限且联合应用协同作用不明显,寻找新的小分子化合物作为已有抗真菌药物的增效剂来发挥协同作用,可成为治疗侵袭性真菌感染的新策略。本文结合本课题组的研究工作及国内外报道的具有协同抗耐药真菌活性的天然小分子化合物的研究工作进行综述,对它们的来源、结构、药理活性和作用机制进行分析,以寻找其中的共性规律,为抗耐药真菌的创新药物研发提供理论基础。

The incidence of systemic fungal infections have increased dramatically, moreover, drug resistance including either primary （intrinsic） or secondary （acquired） resistance, becomes one of the main reasons accounting for the failure of treating invasive fungal infections in the past decades. Nowadays, clinically available antifungal drugs are limited and their combination in antifungal therapy was not effective. It is expected to be a new strategy to synergistically sensitize antifungal drugs against drug-resistant fungi by using new small molecules. Based on the study in our research group and the reported work of others, we reviewed the research of the natural products which have synergistic effect with the antifungal agents against drug-resistant fungi. This review focused on the resource, structure, pharmacological activity, and action mechanism of the compounds, as well as somewhat in common, and would provide theoretical base for seeking new drug against drug-resistance fimgi.