Project description
Computational chemistry in anticancer drug design
Damaging the DNA of cancer cells is one of the most popular chemotherapeutic strategies against cancer. To improve the therapeutic index of DNA-damaging compounds, it is necessary to employ computational chemistry tools. These allow to visualise the damage and repair of the DNA double helix following binding of the drug. Key objectives of the EU-funded SN2DNA project are to evaluate the distorting effects of chemotherapeutic drug-DNA complexes and assess in silico the properties of new drug candidates. This in silico approach has the potential to be implemented in the pipeline of anticancer drug design and discovery.
Objective
Administration of DNA-damaging reagents constitutes one of the most effective chemotherapeutic strategies for the cancer treatment. The families of drugs developed over the years for this purpose are based on second-order nucleophilic substitution (SN2) reactions. Innovative candidates to improve the therapeutic action of these compounds have been designed based on increasing the number of electrophilic positions (En) of the reagent by making n>2. This increased electrophilicity must generate interstrand crosslink adducts that should result in irreversible lesions in the DNA of cancer cells. Computational chemistry tools based on quantum mechanics and molecular modelling, constitute key tools for a better understanding of DNA damage and repair after the formation of the covalently bound complexes that distort the double helix. Thus, the aim of the project described in this proposal is to: 1) compute the structures and evaluate the distorting effects of DNA adducts with polyelectrophilic chemotherapeutic reagents, 2) compute the kinetics of the consecutive SN2 processes (on both carbon atoms and metallic centres) involving interstrand and intrastrand crosslinks and 3) assess in silico the ADME (Adsorption, Distribution, Metabolism and Excretion) properties of the synthesised candidates. Those objectives will be achieved by computing the behaviour of different families of molecules through quantum mechanical - at DFT level of theory- and Molecular Mechanics calculations - based on QM/MM method. Some of these candidates have been synthesised in the laboratories of the hosting group and the corresponding preliminary and promising biological results are already available. The outputs of this project will result in a patent proposal and research articles to be published in high impact journals. Our findings will be open-access available in order to contribute with the research on anticancer drugs design.
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.
- natural sciences physical sciences quantum physics
- medical and health sciences basic medicine medicinal chemistry
- natural sciences biological sciences genetics DNA
- medical and health sciences clinical medicine oncology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2020
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
48940 Leioa
Spain
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.