Synthesis and In Vitro Pharmacological Evaluation of 5,8-Dideaza Analogs of Methotrexate
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 we...
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| Format: | Article |
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MDPI AG
2025-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/30/13/2772 |
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| author | Marta Abellán-Flos Charles Skarbek Dáire J. Gibbons Estelle Rascol Ainhoa García Raphaël Labruère |
| author_facet | Marta Abellán-Flos Charles Skarbek Dáire J. Gibbons Estelle Rascol Ainhoa García Raphaël Labruère |
| author_sort | Marta Abellán-Flos |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-da235de6924543c38cd11f15c5f7243f |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-da235de6924543c38cd11f15c5f7243f2025-08-20T03:28:28ZengMDPI AGMolecules1420-30492025-06-013013277210.3390/molecules30132772Synthesis and In Vitro Pharmacological Evaluation of 5,8-Dideaza Analogs of MethotrexateMarta Abellán-Flos0Charles Skarbek1Dáire J. Gibbons2Estelle Rascol3Ainhoa García4Raphaël Labruère5Institut de Chimie Moléculaire et des Matériaux d’Orsay, Université Paris-Saclay, CNRS UMR 8182, 91400 Orsay, FranceInstitut de Chimie Moléculaire et des Matériaux d’Orsay, Université Paris-Saclay, CNRS UMR 8182, 91400 Orsay, FranceInstitut de Chimie Moléculaire et des Matériaux d’Orsay, Université Paris-Saclay, CNRS UMR 8182, 91400 Orsay, FranceInstitut de Chimie Moléculaire et des Matériaux d’Orsay, Université Paris-Saclay, CNRS UMR 8182, 91400 Orsay, FranceInstitut de Chimie Moléculaire et des Matériaux d’Orsay, Université Paris-Saclay, CNRS UMR 8182, 91400 Orsay, FranceInstitut de Chimie Moléculaire et des Matériaux d’Orsay, Université Paris-Saclay, CNRS UMR 8182, 91400 Orsay, FranceThis 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.https://www.mdpi.com/1420-3049/30/13/2772methotrexatequinazolinecytotoxicityDHFRin vitro metabolism |
| spellingShingle | Marta Abellán-Flos Charles Skarbek Dáire J. Gibbons Estelle Rascol Ainhoa García Raphaël Labruère Synthesis and In Vitro Pharmacological Evaluation of 5,8-Dideaza Analogs of Methotrexate Molecules methotrexate quinazoline cytotoxicity DHFR in vitro metabolism |
| title | Synthesis and In Vitro Pharmacological Evaluation of 5,8-Dideaza Analogs of Methotrexate |
| title_full | Synthesis and In Vitro Pharmacological Evaluation of 5,8-Dideaza Analogs of Methotrexate |
| title_fullStr | Synthesis and In Vitro Pharmacological Evaluation of 5,8-Dideaza Analogs of Methotrexate |
| title_full_unstemmed | Synthesis and In Vitro Pharmacological Evaluation of 5,8-Dideaza Analogs of Methotrexate |
| title_short | Synthesis and In Vitro Pharmacological Evaluation of 5,8-Dideaza Analogs of Methotrexate |
| title_sort | synthesis and in vitro pharmacological evaluation of 5 8 dideaza analogs of methotrexate |
| topic | methotrexate quinazoline cytotoxicity DHFR in vitro metabolism |
| url | https://www.mdpi.com/1420-3049/30/13/2772 |
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