2. Academic Validation
  3. Potent synergistic effect of natural product-inspired Sinomenine derivatives with fluconazole against azole-resistant Candida albicans

Potent synergistic effect of natural product-inspired Sinomenine derivatives with fluconazole against azole-resistant Candida albicans

  • Bioorg Med Chem Lett. 2025 Jun 1:121:130159. doi: 10.1016/j.bmcl.2025.130159.
Wei Liu 1,  Jiayao Du 1,  Zhenzhen Qin 1,  Mei Zhao 1,  Shuaibo Du 1,  Jianwu Xie 1,  Ya Zhang 2,  Mengzhou Wang 3,  Shengzheng Wang 4
Affiliations

Affiliations

  • 1 Faculty of Pharmacy, Shaanxi University of Science and Technology, Xi'an 710021, China.
  • 2 School of Pharmacy, Fourth Military Medical University, Xi'an 710027, China. Electronic address: lmlx2428@163.com.
  • 3 Faculty of Pharmacy, Shaanxi University of Science and Technology, Xi'an 710021, China. Electronic address: 4977@sust.edu.cn.
  • 4 School of Pharmacy, Fourth Military Medical University, Xi'an 710027, China. Electronic address: wangshengzheng001@163.com.
PMID: 40068740 DOI: 10.1016/j.bmcl.2025.130159
Abstract

Candida albicans (C. albicans) is the most common cause of invasive Candida infections worldwide. The acquired resistance of C. albicans to fluconazole, a first-line Antifungal drug, has been frequently reported, posing significant challenges to treatment. Combination therapy has emerged as an effective strategy to combat drug resistance. In this study, we synthesized a series of sinomenine derivatives and evaluated in vitro synergistic activity against azole-resistant C. albicans. The results demonstrated that compound 3ja exhibited a potent synergistic effect with fluconazole against azole-resistant C. albicans. Mechanism studies revealed that the combination of 3ja and FLC significantly induced Reactive Oxygen Species accumulation, disrupted membrane integrity, altered membrane sterols, and promoted Apoptosis in C. albicans.

Keywords

Antifungal activity; Azole-resistant Candida albicans; Sinomenine derivatives; Synergistic effect.

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