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Investigating light-activated therapeutic compounds as antifungal agents.

研究光激活治疗化合物作为抗真菌剂。

基本信息

批准号：
2753345
负责人：
金额：
--
依托单位：
Newcastle University
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2022
资助国家：
英国
起止时间：
2022 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2753345
关键词：
Investigating light activated therapeutic compounds

项目摘要

Fungi are key pathogens of humans, animals and plants. Fungal diseases are intrinsically difficult to treat, there are limited classes of antifungals and the development of resistance is a serious problem. As such, fungal pathogens are threats to human health and food security and there is a need to develop new therapeutic strategies. LightOx has developed a portfolio of small molecule therapeutic compounds which overcome the limitations of current light-based treatments. The compounds have light-activated cytotoxic properties and can be linked to cell-specific targeting macromolecules. The utility of these compounds is being investigated for a range of targets including cancer cells, plants and bacteria. This project builds on a successful pilot study, to determine the antifungal activity of LightOx compounds. Our pilot study revealed that LightOx compounds are readily taken up by fungal cells and has identified compounds with light-dependent inhibitory effects on the growth of the model yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe, and the key human pathogen, Candida albicans. Therefore, the aims of this project are (i) to determine the spectrum of antifungal activity of LightOx compounds and (ii) to use functional genomics and cell biology to inform on their mode of action.

真菌是人类、动物和植物的主要病原体。真菌疾病本质上难以治疗，抗真菌药物种类有限，耐药性的发展是一个严重的问题。因此，真菌病原体是对人类健康和粮食安全的威胁，需要开发新的治疗策略。LightOx开发了一系列小分子治疗化合物，克服了目前光治疗的局限性。该化合物具有光激活的细胞毒性特性，并且可以连接到细胞特异性靶向大分子。这些化合物的效用正在被研究用于一系列靶点，包括癌细胞、植物和细菌。该项目建立在一项成功的试点研究的基础上，以确定LightOx化合物的抗真菌活性。我们的初步研究表明，LightOx化合物很容易被真菌细胞吸收，并且已经鉴定出对模型酵母、酿酒酵母和粟酒裂殖酵母以及关键的人类病原体白色念珠菌的生长具有光依赖性抑制作用的化合物。因此，该项目的目的是（i）确定LightOx化合物的抗真菌活性谱，以及（ii）使用功能基因组学和细胞生物学来了解其作用模式。