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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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.