Covalent Conjugation Strategies for Antifungal Agents: Synthetic Approaches and Therapeutic Potential

IF 3.4 4区医学 Q2 CHEMISTRY, MEDICINAL

ChemMedChem Pub Date : 2025-08-25 DOI:10.1002/cmdc.202500403

Andrzej S. Skwarecki, Marta Skwarecka

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Abstract

The increasing prevalence of invasive fungal infections, alongside rising resistance to conventional antifungal therapies, necessitates the development of improved treatment strategies. This review provides a comprehensive overview of recent advances in the design, synthesis, and biological evaluation of antifungal drug conjugates. Particular emphasis is placed on structural modifications of clinically used antifungal agents—such as azoles, echinocandins, and polyene macrolides—as well as novel conjugates incorporating coumarins, steroids, amino acids, and peptides. Conjugation strategies, including covalent attachment to small molecules, polymers, or bioactive moieties, have been employed to improve pharmacokinetic properties, reduce toxicity, and overcome drug resistance. The synthesis methods and biological profiles of selected conjugates are critically discussed, highlighting their potential as candidates for next-generation antifungal therapeutics. This review underscores the versatility of conjugation chemistry as a promising platform for antifungal drug development.

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抗真菌药物的共价偶联策略：合成方法和治疗潜力。

侵袭性真菌感染的日益流行，以及对传统抗真菌疗法的耐药性上升，需要开发改进的治疗策略。本文综述了抗真菌药物偶联物的设计、合成和生物学评价方面的最新进展。特别强调的是临床使用的抗真菌药物的结构修饰，如唑、棘白菌素和多烯大环内酯，以及结合香豆素、类固醇、氨基酸和肽的新型偶联物。偶联策略，包括与小分子、聚合物或生物活性部分的共价附着，已被用于改善药代动力学性质、降低毒性和克服耐药性。合成方法和选定的缀合物的生物学特性进行了批判性的讨论，突出了它们作为下一代抗真菌治疗药物的候选物的潜力。这篇综述强调了偶联化学作为抗真菌药物开发的一个有前途的平台的多功能性。

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来源期刊

ChemMedChem 医学-药学

CiteScore

6.70

自引率

2.90%

发文量

280

审稿时长

1 months

期刊介绍： Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.