洛沙坦对白色念珠菌生物膜具有抑菌和杀菌作用:针对局部念珠菌病的药物再利用。

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Assay and drug development technologies Pub Date : 2023-05-01 Epub Date: 2023-05-25 DOI:10.1089/adt.2023.013
Vanessa Soares Lara, Rafaela Alves da Silva, Tatiane Ponteado Ferrari, Carlos Ferreira Dos Santos, Sandra Helena Penha de Oliveira
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引用次数: 0

摘要

念珠菌病是最常见的机会性感染之一,临床表现多种多样,包括口腔局部感染。影响肾素-血管紧张素系统靶点的药物可抑制白色念珠菌分泌的天冬氨酸蛋白酶。本研究旨在评估洛沙坦是否对白念珠菌生物膜具有抗菌作用。使用 XTT [2,3-双(2-甲氧基-4-硝基-5-磺酸苯基)-5-[(苯基-氨基)羰基]-2H-氢氧化四氮唑]和菌落形成单位检测法分别评估了存活细胞的代谢活性和白念珠菌生物膜的生长抑制作用。此外,还使用 AlamarBlue 试验评估了药物对人体细胞的细胞毒性。在所有浓度下,这两种药物都能降低真菌的存活率。此外,所有浓度的洛沙坦都能抑制白僵菌生物膜的生长,抑制率从47%到88.5%不等;而阿利吉仑的抑制率从1到10毫克/毫升不等,从16%到97.6%不等。此外,在一定浓度下,这些药物还能维持人体细胞的活力。洛沙坦和阿利吉仑对白僵菌生物膜具有抑菌和杀菌作用,并且与人体细胞兼容。因此,这些降压药可以重新用于干扰念珠菌生物膜的代谢和发展,而念珠菌生物膜与临床形式的念珠菌病广泛相关,包括口腔局部形式的念珠菌病,如义齿口腔炎。
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Losartan Plays a Fungistatic and Fungicidal Activity Against Candida albicans Biofilms: Drug Repurposing for Localized Candidosis.

Candidosis is one of the most frequent opportunistic infections and exhibits variable clinical presentations, including oral localized forms. Drugs affecting the renin-angiotensin system targets inhibit secreted aspartic proteases from Candida albicans. The objective of the study was to evaluate whether losartan has antimicrobial action against C. albicans biofilms. Biofilms were treated with losartan or aliskiren (for comparison) for 24 h. Metabolic activity of viable cells and growth inhibition of C. albicans biofilms were assessed using XTT [2,3-Bis(2-Methoxy-4-Nitro-5-Sulfophenyl)-5-[(Phenyl-Amino)Carbonyl]-2H-Tetrazolium Hydroxide] and colony-forming unit assays, respectively. In addition, the cytotoxicity of the drugs on human cells was evaluated using the AlamarBlue assay. Both drugs decreased fungal viability at all concentrations. In addition, all concentrations of losartan inhibited the growth of C. albicans biofilm, ranging from 47% to 88.5%, whereas aliskiren showed inhibition from 1 to 10 mg/mL, which ranged from 16% to 97.6%. Furthermore, at certain concentrations, these drugs maintained the viability of human cells. Losartan and aliskiren have fungistatic and fungicidal action against C. albicans biofilms and are compatible with human cells. Therefore, these antihypertensive drugs can be repurposed to interfere with the metabolism and development of Candida biofilms, which are widely associated with clinical forms of candidosis, including oral localized forms such as denture stomatitis.

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来源期刊
Assay and drug development technologies
Assay and drug development technologies 医学-生化研究方法
CiteScore
3.60
自引率
0.00%
发文量
33
审稿时长
>12 weeks
期刊介绍: ASSAY and Drug Development Technologies provides access to novel techniques and robust tools that enable critical advances in early-stage screening. This research published in the Journal leads to important therapeutics and platforms for drug discovery and development. This reputable peer-reviewed journal features original papers application-oriented technology reviews, topical issues on novel and burgeoning areas of research, and reports in methodology and technology application. ASSAY and Drug Development Technologies coverage includes: -Assay design, target development, and high-throughput technologies- Hit to Lead optimization and medicinal chemistry through preclinical candidate selection- Lab automation, sample management, bioinformatics, data mining, virtual screening, and data analysis- Approaches to assays configured for gene families, inherited, and infectious diseases- Assays and strategies for adapting model organisms to drug discovery- The use of stem cells as models of disease- Translation of phenotypic outputs to target identification- Exploration and mechanistic studies of the technical basis for assay and screening artifacts
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