Yu Yuming, Chen Peng, Gao Ming, Lan Wei, Sun Shijun, Ma Ziwei, Sultani Rome, Cui Yincang, Umar Muhammad Naveed, Khan Sher Wali, Cai Xiaodong, Liang Zhenjiang, Tan Hui
State Key Laboratory of Chemistry and Utilization of Carbon-Based Energy Resources; College of Chemistry, Xinjiang University, Urumqi 830017, Xinjiang, P. R. China.
Department of Neurosurgery, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518026, China.
ACS Omega. 2022 Apr 19;7(17):14690-14696. doi: 10.1021/acsomega.1c07201. eCollection 2022 May 3.
Although Amphotericin B (AmB) is considered as the "gold standard" treatment for deep fungal infections, owing to its excellent antifungal effect, it often causes severe hemolytic toxicity and nephrotoxicity, which limits its clinical use. We designed and synthesized AmB derivatives by attaching salicylic acid (SA) to the carboxyl group and confirmed their structures using H NMR, C NMR, HR-MS, and IR. We evaluated its biological activity and measured its ultraviolet-visible (UV-vis) absorption spectrum. The AmB-SA conjugates exhibited good antifungal effects against , , and compared with AmB, and the renal cytotoxicity toward HEK 293T cells was significantly reduced, with almost no nephrotoxicity in the therapeutic window of the drug. At the same time, the hemolytic toxicity was significantly reduced. Therefore, modification of AmB by introducing SA is an effective strategy to maintain the broad antifungal activity of AmB and reduce its cytotoxicity. These AmB derivatives could be applied in clinical therapy in the future.
尽管两性霉素B（AmB）因其出色的抗真菌效果而被视为深部真菌感染的“金标准”治疗药物，但它常引发严重的溶血毒性和肾毒性，这限制了其临床应用。我们通过将水杨酸（SA）连接到羧基上设计并合成了AmB衍生物，并使用¹H NMR、¹³C NMR、HR-MS和IR对其结构进行了确认。我们评估了其生物活性并测量了其紫外可见（UV-vis）吸收光谱。与AmB相比，AmB-SA缀合物对[具体真菌名称1]、[具体真菌名称2]和[具体真菌名称3]表现出良好的抗真菌效果，并且对HEK 293T细胞的肾细胞毒性显著降低，在药物治疗窗口内几乎没有肾毒性。同时，溶血毒性也显著降低。因此，通过引入SA对AmB进行修饰是维持AmB广泛抗真菌活性并降低其细胞毒性的有效策略。这些AmB衍生物未来可应用于临床治疗。
