ArticleMolecules (Basel, Switzerland)2025
Synthesis and In Vitro Pharmacological Evaluation of 5,8-Dideaza Analogs of Methotrexate.
Article in Molecules (Basel, Switzerland), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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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.
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