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Re-designing environmentally persistent pharmaceutical pollutant through programmed inactivation: The case of methotrexate
Environmental emission of pharmaceutical pollutants notably causes the contamination of aquatic ecosystems and drinking water. Typically, reduction of these pollutants in the environment is mostly managed by ameliorated wastewater treatments. Here, we report a method for the eco-design of drugs thro...
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Published in: | Chemosphere (Oxford) 2022-11, Vol.306, p.135616-135616, Article 135616 |
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creator | Espinosa, Anaïs Rascol, Estelle Abellán Flos, Marta Skarbek, Charles Lieben, Pascale Bannerman, Eva Martinez, Alba Diez Pethe, Stéphanie Benoit, Pierre Nélieu, Sylvie Labruère, Raphaël |
description | Environmental emission of pharmaceutical pollutants notably causes the contamination of aquatic ecosystems and drinking water. Typically, reduction of these pollutants in the environment is mostly managed by ameliorated wastewater treatments. Here, we report a method for the eco-design of drugs through the introduction within the molecular structure of a sensitive chemical group responsive to water treatments. The new drugs are thus programmed to fragment more easily and quickly than the original drugs. In this “retro catabolic drug design” strategy, methotrexate was used as drug model and an ether analog displaying a similar pharmacological profile was selected. Using photo-irradiation experiments at 254 nm, a representative drinking water treatment process, the identified transformation products were predominantly obtained from the expected molecular scission. Moreover, a faster kinetics of degradation was measured for the ether analog as compared to methotrexate and its transformation products were far less cytotoxic.
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•The strategy of “retro catabolic drug design” is disclosed for the programmed/improved inactivation of drugs.•The drug model is methotrexate and three analogs were synthesized.•An ether analog displaying similar antitumor activity was selected and its better human metabolic stability was demonstrated.•Using photo-irradiation, the identified transformation products were mostly obtained from the expected molecular scission.•A faster kinetics of degradation was measured for the ether analog and its transformation products were less cytotoxic. |
doi_str_mv | 10.1016/j.chemosphere.2022.135616 |
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[Display omitted]
•The strategy of “retro catabolic drug design” is disclosed for the programmed/improved inactivation of drugs.•The drug model is methotrexate and three analogs were synthesized.•An ether analog displaying similar antitumor activity was selected and its better human metabolic stability was demonstrated.•Using photo-irradiation, the identified transformation products were mostly obtained from the expected molecular scission.•A faster kinetics of degradation was measured for the ether analog and its transformation products were less cytotoxic.</description><identifier>ISSN: 0045-6535</identifier><identifier>EISSN: 1879-1298</identifier><identifier>DOI: 10.1016/j.chemosphere.2022.135616</identifier><identifier>PMID: 35810859</identifier><language>eng</language><publisher>Elsevier Ltd</publisher><subject>Chemical Sciences ; Eco-design ; Environmental Engineering ; Environmental Sciences ; Medicinal Chemistry ; Pharmaceutical pollutants ; Photodegradation ; Retro catabolic drug design ; Structural identification</subject><ispartof>Chemosphere (Oxford), 2022-11, Vol.306, p.135616-135616, Article 135616</ispartof><rights>2022 Elsevier Ltd</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-831aa1083d1f33f224e878543b47978fb6f4219d2fefbbd0a3d705c9762e807b3</citedby><cites>FETCH-LOGICAL-c439t-831aa1083d1f33f224e878543b47978fb6f4219d2fefbbd0a3d705c9762e807b3</cites><orcidid>0000-0003-3683-2768 ; 0000-0002-3677-7300 ; 0000-0002-2301-6107 ; 0000-0003-0054-2064</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://hal.science/hal-03826123$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Espinosa, Anaïs</creatorcontrib><creatorcontrib>Rascol, Estelle</creatorcontrib><creatorcontrib>Abellán Flos, Marta</creatorcontrib><creatorcontrib>Skarbek, Charles</creatorcontrib><creatorcontrib>Lieben, Pascale</creatorcontrib><creatorcontrib>Bannerman, Eva</creatorcontrib><creatorcontrib>Martinez, Alba Diez</creatorcontrib><creatorcontrib>Pethe, Stéphanie</creatorcontrib><creatorcontrib>Benoit, Pierre</creatorcontrib><creatorcontrib>Nélieu, Sylvie</creatorcontrib><creatorcontrib>Labruère, Raphaël</creatorcontrib><title>Re-designing environmentally persistent pharmaceutical pollutant through programmed inactivation: The case of methotrexate</title><title>Chemosphere (Oxford)</title><description>Environmental emission of pharmaceutical pollutants notably causes the contamination of aquatic ecosystems and drinking water. Typically, reduction of these pollutants in the environment is mostly managed by ameliorated wastewater treatments. Here, we report a method for the eco-design of drugs through the introduction within the molecular structure of a sensitive chemical group responsive to water treatments. The new drugs are thus programmed to fragment more easily and quickly than the original drugs. In this “retro catabolic drug design” strategy, methotrexate was used as drug model and an ether analog displaying a similar pharmacological profile was selected. Using photo-irradiation experiments at 254 nm, a representative drinking water treatment process, the identified transformation products were predominantly obtained from the expected molecular scission. Moreover, a faster kinetics of degradation was measured for the ether analog as compared to methotrexate and its transformation products were far less cytotoxic.
[Display omitted]
•The strategy of “retro catabolic drug design” is disclosed for the programmed/improved inactivation of drugs.•The drug model is methotrexate and three analogs were synthesized.•An ether analog displaying similar antitumor activity was selected and its better human metabolic stability was demonstrated.•Using photo-irradiation, the identified transformation products were mostly obtained from the expected molecular scission.•A faster kinetics of degradation was measured for the ether analog and its transformation products were less cytotoxic.</description><subject>Chemical Sciences</subject><subject>Eco-design</subject><subject>Environmental Engineering</subject><subject>Environmental Sciences</subject><subject>Medicinal Chemistry</subject><subject>Pharmaceutical pollutants</subject><subject>Photodegradation</subject><subject>Retro catabolic drug design</subject><subject>Structural identification</subject><issn>0045-6535</issn><issn>1879-1298</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNqNkU-P0zAQxS0EYsvCdzA3OKT4T5zY3FbVwiJVQkLL2XKccePKiYPtVCyfnlRBiCOn0cy89zSjH0JvKdlTQpsP570dYIx5HiDBnhHG9pSLhjbP0I7KVlWUKfkc7QipRdUILm7Qq5zPhKxmoV6iGy4kJVKoHfr1Daoesj9NfjphmC4-xWmEqZgQnvAMKftc1hbPg0mjsbAUb03AcwxhKWZdlCHF5TTgOcVTMuMIPfaTscVfTPFx-ogfB8DWZMDR4RHKEEuCn6bAa_TCmZDhzZ96i75_un88PFTHr5-_HO6Ola25KpXk1Jj1Wt5Tx7ljrAbZSlHzrm5VK13XuJpR1TMHrut6YnjfEmFV2zCQpO34LXq_5Q4m6Dn50aQnHY3XD3dHfZ0RLllDGb_QVftu067f_FggFz36bCEEM0FcsmaNlETKRopVqjapTTHnBO5vNiX6ikmf9T-Y9BWT3jCt3sPmhfXvi4eks_UwWeh9Alt0H_1_pPwGcDGicw</recordid><startdate>20221101</startdate><enddate>20221101</enddate><creator>Espinosa, Anaïs</creator><creator>Rascol, Estelle</creator><creator>Abellán Flos, Marta</creator><creator>Skarbek, Charles</creator><creator>Lieben, Pascale</creator><creator>Bannerman, Eva</creator><creator>Martinez, Alba Diez</creator><creator>Pethe, Stéphanie</creator><creator>Benoit, Pierre</creator><creator>Nélieu, Sylvie</creator><creator>Labruère, Raphaël</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0003-3683-2768</orcidid><orcidid>https://orcid.org/0000-0002-3677-7300</orcidid><orcidid>https://orcid.org/0000-0002-2301-6107</orcidid><orcidid>https://orcid.org/0000-0003-0054-2064</orcidid></search><sort><creationdate>20221101</creationdate><title>Re-designing environmentally persistent pharmaceutical pollutant through programmed inactivation: The case of methotrexate</title><author>Espinosa, Anaïs ; 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Typically, reduction of these pollutants in the environment is mostly managed by ameliorated wastewater treatments. Here, we report a method for the eco-design of drugs through the introduction within the molecular structure of a sensitive chemical group responsive to water treatments. The new drugs are thus programmed to fragment more easily and quickly than the original drugs. In this “retro catabolic drug design” strategy, methotrexate was used as drug model and an ether analog displaying a similar pharmacological profile was selected. Using photo-irradiation experiments at 254 nm, a representative drinking water treatment process, the identified transformation products were predominantly obtained from the expected molecular scission. Moreover, a faster kinetics of degradation was measured for the ether analog as compared to methotrexate and its transformation products were far less cytotoxic.
[Display omitted]
•The strategy of “retro catabolic drug design” is disclosed for the programmed/improved inactivation of drugs.•The drug model is methotrexate and three analogs were synthesized.•An ether analog displaying similar antitumor activity was selected and its better human metabolic stability was demonstrated.•Using photo-irradiation, the identified transformation products were mostly obtained from the expected molecular scission.•A faster kinetics of degradation was measured for the ether analog and its transformation products were less cytotoxic.</abstract><pub>Elsevier Ltd</pub><pmid>35810859</pmid><doi>10.1016/j.chemosphere.2022.135616</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-3683-2768</orcidid><orcidid>https://orcid.org/0000-0002-3677-7300</orcidid><orcidid>https://orcid.org/0000-0002-2301-6107</orcidid><orcidid>https://orcid.org/0000-0003-0054-2064</orcidid><oa>free_for_read</oa></addata></record> |
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source | ScienceDirect Freedom Collection 2022-2024 |
subjects | Chemical Sciences Eco-design Environmental Engineering Environmental Sciences Medicinal Chemistry Pharmaceutical pollutants Photodegradation Retro catabolic drug design Structural identification |
title | Re-designing environmentally persistent pharmaceutical pollutant through programmed inactivation: The case of methotrexate |
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