Year: 2025
Type: article
Abstract: This study describes the synthesis of a series of dideaza analogs of methotrexate and their preliminary pharmacological and metabolic evaluation. The 5,8-dideazamethotrexate was efficiently obtained in five steps using a new synthetic route. Oxygenated and thiolated analogs of dideazamethotrexate were prepared following the devised pathway. Their cytotoxicity was studied in the A549 lung cancer cell line, as well as their DHFR dihydrofolate reductase inhibition activity and in vitro metabolism. The two new analogs showed strong activity on cancer cells and the enzymatic target. These compounds were not metabolized, a clear advantage over methotrexate, which is rapidly converted to the toxic metabolite 7-hydroxymethotrexate.
Source: Molecules
Institutions: Centre National de la Recherche Scientifique, Université Paris-Saclay, Institut de Chimie Moléculaire et des Matériaux d'Orsay, Université de Bordeaux, Chimie et Biologie des Membranes et des Nanoobjects, Institut Polytechnique de Bordeaux, Inserm, Université Paris Sciences et Lettres, Chimie et Modélisation pour la Biologie du Cancer, Institut Curie
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,258
OpenAlex ID: W4411803185