H2020Индивидуална стипендия2016–2018

MESO-JBIR-102 · Development of the aza-Prins reaction; synthesis and biological evaluation of JBIR-102

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

Период: 2016-07-01 → 2018-10-16
Финансиране от ЕС: 195 455 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Природното соединение JBIR-102 и нов химичен метод за създаване на азотни структури се изучават за борба с мезотелиома. Работата е важна, защото този агресивен рак на белия дроб няма ефективни лекарства и липсват достатъчно изследвания за него.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Development of the aza-Prins reaction; synthesis and biological evaluation of JBIR-102

Human malignant pleural mesothelioma is an aggressive (fatal) lung cancer which is always associated with previous asbestos exposure. Typically symptoms do not appear until 35-40 years after the original exposure, with life expectancy then 12-18 months. There is no known cure for mesothelioma: traditional chemotherapeutic cancer treatments have had little impact on the disease and radiotherapy or partial pleurectomy have only very limited impact on life expectancy. However, very little in the way of mesothelioma research is taking place, as it is frequently not considered to be a ‘big enough market’ (<1% of all cancers in the U.K., approximately 2300 deaths per annum). Consequently there are currently no novel drugs in development for this disease. A second reason is that there have been no reported good lead compounds as a starting point for the drug discovery process. Hence any projects - such as this one - looking to address our fundamental knowledge of mesothelioma will be of significant societal impact. This project aimed to study a novel, newly isolated natural product, named JBIR-102, and its associated anti-mesothelioma activity. This was addressed in two ways: first by the development of the aza-Prins reaction - a novel piece of synthetic chemistry to prepare nitrogen-containing heterocyclic structures and second to apply this developed method to the synthesis of JBIR-102. Within this, the first aim - developing the aza-Prins reaction - was achieved very successfully and the second half of the project was well advanced at the end of the contract.

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

Цел на проекта

Human malignant pleural mesothelioma is an aggressive (fatal) lung cancer which is always associated with previous asbestos exposure. Typically symptoms do not appear until 35-40 years after the original exposure, with life expectancy then 12-18 months. Given the great use of asbestos during the 20th century and this long latency period, it is no surprise that cases of mesothelioma continue to rise. There is no known cure for mesothelioma: traditional chemotherapeutic treatments have had little impact on the disease and radiotherapy or partial pleurectomy have only very limited impact on life expectancy. However, very little in the way of mesothelioma research is taking place, as it is frequently not considered to be a ‘big enough market’ (<1% of all cancers in the U.K., approx. 2300 deaths per annum) and consequently there are currently no drugs in development for this disease. A second reason for this is that there have been no reported good lead compounds (natural products) as a starting point for the drug discovery process. Until now.There are now a very small number of natural products which demonstrate activity against mesothelioma. First reported in 2012, and isolated from Saccharopolyspora sp. RL78, the natural product termed JBIR-102 possesses a unique structural architecture, and is only the third natural product to be isolated to exhibit activity against human malignant pleural mesothelioma.The aza-silyl-Prins reaction has been developed within our research group as a rapid method to prepare aza-bicycles – structural architectures found in many alkaloids and natural products, and crucially at the centre of JBIR-102. The aim of the project, therefore, is to optimise the aza-silyl-Prins reaction and then investigate its application in the synthesis of JBIR-102. A collaboration with a specialist cancer biology group will see all the compounds prepared evaluated against mesothelioma cell lines. This will be the first study of this kind.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITY OF GREENWICH · LondonКоординаторОбединеното кралство