Chen Xueqi, Zhang Zewen, Chen Zuozhong, Li Yiman, Su Shan, Sun Shujuan
Department of Pharmacy, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
School of Pharmaceutical Sciences, Shandong University, Jinan, China.
Front Microbiol. 2020 Mar 17;11:296. doi: 10.3389/fmicb.2020.00296. eCollection 2020.
In recent years, fungal infections have become a serious health problem. are considered as the fourth most common isolates associated with approximately 40% mortality in bloodstream infections among hospitalized patients. Due to various limitations of classical antifungals used currently, such as limited kinds of drugs, inevitable toxicities, and high price, there is an urgent need to explore new antifungal agents based on novel targets. Generally, nutrient metabolism is involved with fungal virulence, and glucose is one of the important nutrients in . can obtain and metabolize glucose through a variety of pathways; in theory, many enzymes in these pathways can be potential targets for developing new antifungal agents, and several studies have confirmed that compounds which interfere with alpha-glucosidase, acid trehalase, trehalose-6-phosphate synthase, class II fructose bisphosphate aldolases, and glucosamine-6-phosphate synthase in these pathways do have antifungal activities. In this review, the glucose metabolism pathways in , the potential antifungal targets based on these pathways, and some compounds which have antifungal activities by inhibiting several enzymes in these pathways are summarized. We believe that our review will be helpful to the exploration of new antifungal drugs with novel antifungal targets.
近年来,真菌感染已成为一个严重的健康问题。它们被认为是第四大常见分离菌,在住院患者的血流感染中死亡率约为40%。由于目前使用的传统抗真菌药物存在各种局限性,如药物种类有限、不可避免的毒性和高昂的价格,迫切需要探索基于新靶点的新型抗真菌药物。一般来说,营养物质代谢与真菌毒力有关,葡萄糖是其中重要的营养物质之一。真菌可以通过多种途径获取和代谢葡萄糖;理论上,这些途径中的许多酶都可能成为开发新型抗真菌药物的潜在靶点,并且一些研究已经证实,干扰这些途径中α-葡萄糖苷酶、酸性海藻糖酶、海藻糖-6-磷酸合酶、II类果糖双磷酸醛缩酶和葡糖胺-6-磷酸合酶的化合物确实具有抗真菌活性。在这篇综述中,总结了真菌中的葡萄糖代谢途径、基于这些途径的潜在抗真菌靶点以及一些通过抑制这些途径中的几种酶而具有抗真菌活性的化合物。我们相信,我们的综述将有助于探索具有新型抗真菌靶点的新型抗真菌药物。