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

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-03-09 DOI:10.1016/j.bmcl.2025.130159

Wei Liu , Jiayao Du , Zhenzhen Qin , Mei Zhao , Shuaibo Du , Jianwu Xie , Ya Zhang , Mengzhou Wang , Shengzheng Wang

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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.

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天然产物启发青藤碱衍生物与氟康唑对耐唑白色念珠菌的有效协同作用。

白色念珠菌是世界范围内侵袭性念珠菌感染最常见的原因。白色念珠菌对一线抗真菌药物氟康唑的获得性耐药性经常被报道，给治疗带来了重大挑战。联合治疗已成为对抗耐药性的有效策略。在本研究中，我们合成了一系列青藤碱衍生物，并评估了其体外对耐唑白色念珠菌的协同作用。结果表明，化合物3ja与氟康唑对耐唑白色念珠菌具有较强的协同作用。机制研究表明，3ja和FLC联合作用可显著诱导白念珠菌活性氧积累，破坏膜完整性，改变膜固醇，促进细胞凋亡。

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来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.