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...

Full description

Saved in:
Bibliographic Details
Published in:Chemosphere (Oxford) 2022-11, Vol.306, p.135616-135616, Article 135616
Main Authors: Espinosa, Anaïs, Rascol, Estelle, Abellán Flos, Marta, Skarbek, Charles, Lieben, Pascale, Bannerman, Eva, Martinez, Alba Diez, Pethe, Stéphanie, Benoit, Pierre, Nélieu, Sylvie, Labruère, Raphaël
Format: Article
Language:English
Subjects:
Chemical Sciences
Eco-design
Environmental Engineering
Environmental Sciences
Medicinal Chemistry
Pharmaceutical pollutants
Photodegradation
Retro catabolic drug design
Structural identification
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0045-6535
1879-1298
DOI:10.1016/j.chemosphere.2022.135616