Abstract：
Invasive fungal diseases (IFDs) are becoming increasingly acknowledged as a significant concern linked to heightened rates of morbidity and mortality. Regrettably, the available antifungal therapies for managing IFDs are constrained. Emerging evidence indicates that enolase holds promise as a potential target protein for combating IFDs; however, there is currently a deficiency in antifungal medications specifically targeting enolase. This study establishes that isobavachalcone (IBC) exhibits noteworthy antifungal efficacy both in vitro and in vivo. Moreover, our study has demonstrated that IBC effectively targets Eno1 in Candida albicans (CaEno1), resulting in the suppression of the glycolytic pathway. Additionally, our research has indicated that IBC exhibits a higher affinity for CaEno1 compared to human Eno1 (hEno1), with the presence of isoprenoid in the side chain of IBC playing a crucial role in its ability to inhibit enolase activity. These findings contribute to the comprehension of antifungal approaches that target Eno1, identifying IBC as a potential inhibitor of Eno1 in human pathogenic fungi.
摘要：
侵袭性真菌病（IFD）越来越被认为是与发病率和死亡率升高有关的重要问题。遗憾的是,用于管理IFD的可用抗真菌疗法受到限制.新的证据表明，烯醇化酶有望成为对抗IFD的潜在靶蛋白；然而，目前存在特异性针对烯醇化酶的抗真菌药物缺乏。这项研究表明，异叶阿瓦卡酮（IBC）在体外和体内均表现出值得注意的抗真菌功效。此外，我们的研究表明，IBC有效地靶向白色念珠菌的Eno1（CaEno1），导致糖酵解途径的抑制。此外,我们的研究表明，与人类Eno1（hEno1）相比，IBC对CaEno1具有更高的亲和力，IBC侧链中类异戊二烯的存在在其抑制烯醇化酶活性的能力中起着至关重要的作用。这些发现有助于理解靶向Eno1的抗真菌方法，确定IBC是人类病原真菌中Eno1的潜在抑制剂。
