CHR3/Caerulomycin A类化合物抗白念珠菌 活性及靶标机制研究

Study on Antifungal Activity and Target Mechanism of CHR3/Caerulomycin A Compounds against Candida albicans

摘要: 临床耐药菌的出现是当前白念珠菌(Candida albicans)感染治疗的困境，寻找具有全新靶点的新型抗真菌化合物，可以解决当前抗真菌药物选择有限的问题。天然产物一直是新药研发，特别是抗真菌药物研发的重要资源。海洋微生物来源的CHR3/青灰霉素A (Caerulomycin A, CaeA)化合物，是一类具有2,2′-联吡啶核心结构的天然产物，拥有抗细菌、抗真菌、抗肿瘤和免疫调节活性。现阶段针对该类化合物的机制研究主要集中在抗肿瘤及免疫调节活性方面，在白念珠菌中的直接作用蛋白和抑菌分子机制仍未被探究。本文系统整合该类化合物在分子结构改造、抗真菌活性评价、潜在靶标挖掘以及作用机制解析等方面的研究进展，用以评估其发展为抗白念珠菌先导化合物的可能性，也为临床解决白念珠菌耐药问题提供理论参考。

Abstract: The widespread emergence of clinical drug-resistant strains has become a major therapeutic challenge for Candida albicans infections. Discovery of new antifungal candidates with innovative molecular targets offers a promising strategy to overcome the limitations of currently available antifungal agents. Natural products serve as a valuable reservoir for new drug research and development, especially for antifungal drug screening. CHR3/Caerulomycin A (CaeA), isolated from marine microorganisms, is a natural product featuring a characteristic 2,2′-bipyridine scaffold and exhibits prominent antibacterial, antifungal, antitumor and immunomodulatory properties. Existing mechanistic studies on CaeA and its analogues predominantly focus on their antitumor and immunomodulatory effects, whereas their direct target proteins and underlying antifungal mechanisms against C. albicans remain unclarified. This review systematically summarizes the research advances of CaeA-type compounds in structural modification, antifungal activity evaluation, potential target mining and molecular mechanism exploration. It further evaluates their feasibility as lead compounds for anti-C. albicans drug development, and provides theoretical insights for tackling clinical C. albicans drug resistance.