H2020Индивидуална стипендия2018–2020

TSPO METALLODRUGS · Novel, highly effective and selective anticancer metallodrugs

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2018-02-01 → 2020-01-31
Финансиране от ЕС: 175 866 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Златни съединения, свързани с протеина TSPO, се тестват като средство за насочване на лекарствата директно към митохондриите на раковите клетки. Това помага за преодоляване на лекарствената резистентност и активиране на процесите по унищожаване на туморните клетки.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Novel, highly effective and selective anticancer metallodrugs

This project was aimed at the development of novel, highly effective anticancer metallodrugs that selectively target the mitochondria of cancer cells by combining the favourable cytotoxic properties of gold with the capability of TSPO binders to act as delivery vehicles for antimitochondrial agents. Cancer cells becoming resistant in the course of treatment is a major challenge in cancer chemotherapy. Anticancer agents that target the mitochondria have the potential to bypass resistance mechanisms and to (re )activate cell death pathways that are mutated or lacking in cancer cells. They are also anticipated to act selectively on tumor cells, as these have a deregulated mitochondrial metabolism. TSPO is a relatively small protein located at the outer mitochondrial membrane and is overexpressed in many tumors. It plays a fundamental role in mitochondrial biochemistry and has a regulatory function in mitochondria-mediated cell death pathways. Thioredoxin reductase (TrxR) is a key enzyme for the maintenance of the cellular redox balance and has a mitochondrial isoform. Its inhibition leads to an increase in reactive oxygen species (ROS) and to a decrease in mitochondrial thiols, both events that trigger cell death. The antitumor activity of many gold complexes is due to the ability of gold(I) to inhibit TrxR.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Dr. Leila Tabrizi, an Iranian national, is making an application to this programme to carry out a 24 months project in the area of medicinal chemistry in the group of Dr. A. Erxleben at the National University of Ireland, Galway.The objective of this proposal is the synthesis of novel gold anticancer drugs that simultaneously target two mitochondrial proteins that are associated with cancer progression. Gold(III) complexes will be designed that recognize the translocator protein which is overexpressed in various tumour types and that release the metal upon intracellular reduction to gold(I), a known inhibitor of thioredoxin reductase. Binding of the carrier ligand to the translocator protein and inhibition of thioredoxin reductase will induce cell death pathways in a synergistic manner, thus leading to highly effective and selective anticancer action. Detailed in vitro biological studies will be performed to evaluate the potential of the new anticancer drug candidates, to establish structure-activity relationships and to fully understand their mode of action. The researcher has already an excellent background in coordination chemistry and this project will allow her to deepen and expand her skills in synthetic chemistry, to enter into the biological field by receiving relevant training in cell and biological techniques and to establish important academic and industrial collaborations.The researcher who has recently been awarded a Government of Ireland Postdoctoral Fellowship proposes to carry out further research training at NUI Galway which is strategically developing strength in Biomedical Research and Cancer, one of the most important and challenging branches of Chemistry/Biochemistry in Europe. NUI Galway will also provide training in transferable skills and mentoring to the researcher. Both the scientific and personal training will contribute to her personal development and will allow her to reach professional maturity as an independent researcher.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITY OF GALWAY · GalwayКоординаторИрландия