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Chemical and biological investigations of new vanadium compounds: determining their potential in the treatment of cancer

新钒化合物的化学和生物学研究：确定其治疗癌症的潜力

基本信息

批准号：
MR/T041315/1
负责人：
Rianne Lord
金额：
$ 124.75万
依托单位：
University of East Anglia
依托单位国家：
英国
项目类别：
Fellowship
财政年份：
2021
资助国家：
英国
起止时间：
2021 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FT041315%2F1
关键词：
Chemical biological investigations new vanadium

项目摘要

Globally, the treatment of cancer is a substantial economic burden and the effects of cancer have a detrimental impact on the lives of patients and their families, potentially leading to further physical and mental illnesses. The current clinically used metal-based compounds (e.g. cisplatin, oxaliplatin and carboplatin) work by targeting DNA, however, they do not distinguish between cancerous and normal cells. They lead to adverse side effects, including renal failure, neurotoxicity and nausea. Many of the tumours become resistant to these platinum drugs, therefore, there is an urgent need for new drugs which selectively target and eradicate the cancerous cells, whilst minimising the associated side effects.The PI's recently published work highlighted new vanadium drugs which are more active than the clinically used platinum drugs and more selective for cancerous cells. Importantly, the ligands can be modified to incorporate a wide range of functionalities and allow us to determine structure-activity relationships. Also, the complexation of these ligands with vanadium will use our own literature methods, which will allow effective and efficient establishment of compound libraries. The proposed research will also investigate the drugs' distribution and accumulation within cells, and provide insights to the cellular targets and modes of actions. Furthermore, the drugs' activities will be measured in 3D cell culture models, as their environment is closer in nature to real-life tumours. This will enable the PI to identify more suitable and selective drugs, which can be taken towards clinical trials. Overall, this cheap and straight-forward drug design, coupled with in depth "tumour-like" studies, will provide new alternatives to cost-effective and targeted treatment.

在全球范围内，癌症的治疗是一个巨大的经济负担，癌症的影响对患者及其家人的生活产生不利影响，可能导致进一步的身体和精神疾病。目前临床上使用的金属基化合物（例如顺铂、奥沙利铂和卡铂）通过靶向DNA起作用，然而，它们不能区分癌细胞和正常细胞。它们会导致不良副作用，包括肾衰竭、神经毒性和恶心。许多肿瘤对这些铂类药物产生耐药性，因此迫切需要选择性靶向和根除癌细胞的新药，同时将相关副作用降至最低。PI最近发表的工作重点是新的钒药物，这些药物比临床使用的铂类药物更有效，对癌细胞更具选择性。重要的是，配体可以被修饰以引入广泛的功能，并允许我们确定结构-活性关系。此外，这些配体与钒的络合将使用我们自己的文献方法，这将允许有效和高效地建立化合物库。拟议的研究还将调查药物在细胞内的分布和积累，并提供对细胞靶点和作用模式的见解。此外，这些药物的活性将在3D细胞培养模型中进行测量，因为它们的环境在本质上更接近真实的肿瘤。这将使PI能够识别更合适和更有选择性的药物，可以用于临床试验。总的来说，这种廉价而直接的药物设计，加上深入的“肿瘤样”研究，将为具有成本效益和靶向治疗提供新的替代方案。