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植物源组蛋白乙酰转移酶抑制剂的再利用:一种针对耐药真菌生物膜的新型治疗策略综述。

Repurposing Plant-Based Histone Acetyltransferase Inhibitors: A Review of Novel Therapeutic Strategies Against Drug-Resistant Fungal Biofilms.

机构信息

Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Chengalpattu District, Kattankulathur, Tamil Nadu, 603 203, India.

School of Chemical Engineering, Yeungnum University, Gyeongsan, 38541, Republic of Korea.

出版信息

Curr Microbiol. 2024 Nov 12;82(1):1. doi: 10.1007/s00284-024-03971-8.

Abstract

The rapid emergence of drug-resistant fungal strains necessitates the development of novel therapeutic approaches for battling biofilm-related infections. Biofilms, efflux pumps, and suppression of virulence traits in pathogenic yeasts are governed by epigenetic enzymes, namely, histone acetyltransferases (HATs) and histone deacetylases (HDACs). The review article is focused on the use of histone acetyltransferase inhibitors (HATi), a mechanism-based epidrug that inactivates the regular function of HATs. With an emphasis on specific plant-based HATi and their Structure-Activity Relationship (SAR), the review enumerates the extensive list of anticancer HATi that can be screened for antifungal activities. By repurposing these anticancer HATi, this approach may help generate broad-spectrum antifungal medications that highlight common biological pathways between fungus and cancer, possibly revolutionizing both treatment domains.

摘要

耐药真菌菌株的迅速出现,需要开发新的治疗方法来对抗生物膜相关感染。生物膜、外排泵以及致病性酵母菌毒力特性的抑制受表观遗传酶调控,即组蛋白乙酰转移酶(HATs)和组蛋白去乙酰化酶(HDACs)。本文重点讨论了组蛋白乙酰转移酶抑制剂(HATi)的应用,HATi 是一种基于机制的前药,可使 HATs 的常规功能失活。本文特别强调了特定的植物来源的 HATi 及其结构-活性关系(SAR),并列举了大量可用于筛选抗真菌活性的抗癌 HATi。通过重新利用这些抗癌 HATi,这种方法可能有助于生成广谱抗真菌药物,突出真菌和癌症之间的共同生物学途径,可能会彻底改变这两个治疗领域。

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