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Master Thesis

Validation d'une méthode de déreplication de substances naturelles marines

Abstract : Rising incidence of cancers and ever-growing microbial infections are the main concerns of modern medicine, coevolving with the respective drug targeting resistances. This “growing health crisis”, as defined by the World Health Organization in 2014, prompts researchers to find new resources of drug leads. Despite the large number of terrestrial natural products derivatives approved as pharmaceutics, industry has reduced its reliance on it, mostly due to the high rate of rediscovery of known compounds. Therefore, academicians and private industry have turned their efforts toward exploring the marine world as new sources of bioactive molecules. We contributed to this effort in participating in a research project named PharmaSea, based on the bio discovery, identification and development of new substances from marine organisms. The key step to successful drug bio discovery from marine sources is the rapid identification of the known compounds before isolating them. Called dereplication, this approach is essential to assess chemical novelty of crude extracts and their fractions. The profusion of data sets and the lack of confirmatory data make this task arduous. Different strategies of dereplication procedures involving Liquid chromatography coupled with High Resolution Mass Spectrometry are thus emerging. In this regard, we investigated the PharmaSea dereplication method on 21 tunicates extracts. This method combines the ACDLabs IntelliXtract software with the MarinLit database from the Royal Society of Chemistry to dereplicate mass data. Nuclear Magnetic Resonance was also used to streamline the prioritization of samples to study to validate the method. The most interesting sample according to these strategies was selected for further purification leading to the isolation of seven compounds of which five are new as evidence of the success of the method.
Document type :
Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-01500339
Contributor : Jean-Hugues Morneau <>
Submitted on : Monday, April 3, 2017 - 10:17:11 AM
Last modification on : Wednesday, July 15, 2020 - 8:56:03 AM
Long-term archiving on: : Tuesday, July 4, 2017 - 12:43:45 PM

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  • HAL Id : dumas-01500339, version 1

Citation

Léonie Pellissier. Validation d'une méthode de déreplication de substances naturelles marines. Sciences pharmaceutiques. 2017. ⟨dumas-01500339⟩

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