Objective
The natural products neocarzinostatin, esperamicin, calichemicin, dynemicin, and Research objectives and content kedarcidin represent so of the most promising leads for the development of potent anti-cancer agents. However, none of these compounds can be administered as such because they are strong cell poisons. Therefore, a challenging task in medicinal chemistry today is to synthesize analogs of these compounds which conserve their striking antitumor activity but are free from adverse side effects. The project proposed by Prof. Bruckner will contribute to solving this task by developing a synthetic route to a bioactive structural analog 1 of the least investigated member of these natural products, i.e. to the pharmacophore 2 of neocarzinostatin. Me> OMe
Ring strain is decreased and hence stability increased in 1 vs. 2. Almost all other structural features of 2 are preserved in 1, except the sugar moiety. It is therefore expected that thiols react with compound 1 initially in very much the same way as very recently discovered in the case of 2. But importantly, other than 2 compound I should subsequently deliver - as specified in the detailed description of this work biradicals which cleave DNA andy destroy cancerous cells thereb. In-vivo and invitro DNA-cleavage essays will be performed in collaboration with specialists. Training content objective, benefit and expected impact) The goal of my postdoctoral stay is to synthesize the designed pharmacophor 1. The intended work will therefore deepen my acquaintance with modern synthetic methodology. This work will also expose myself for the first time to the particular difficulties of performing a true multistep synthesis. The prospect to synthesize with my own hands a compound which might even become an antitumor antibiotic in a not too optimistic scenario is a special motivation. In addition I consider the intended research as a good opportunity to read more about medicinal chemistry than previously. Last but not least it will be a first-time experience for me having compounds from my bench top tested for cytotoxicity in general (by Prof. Tietze, University of Gottingen) and specifically for their DNA-damaging potential (by Prof. Giese, University of Basel); this sounds like exciting interdisciplinary work.
Links with industry / industrial relevance (22) Whether the intended work has the desired impact - to contribute to the improvement of the chemotherapy of cancer - depends on how quickly the intended synthesis can be realized and on the outcome of the biological tests. Clearly, as soon as promising prelimary results show up, we would explore the possibility of a collaboration with a pharmaceutical company.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine medicinal chemistry
- natural sciences biological sciences genetics DNA
- humanities languages and literature literature studies literary genres essays
- medical and health sciences clinical medicine oncology
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
37077 Göttingen
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.