Synthesis and Biological Evaluation of Novel Antifolate Analogs as Potential Anticancer Treatment

Title:Synthesis and Biological Evaluation of Novel Antifolate Analogs as Potential Anticancer Treatment

Volume: 13 Issue: 2

Author(s): Dan F. Stoicescu and Maria Rotaru

Affiliation:

Keywords: Antifolate inhibitors, Antitumor activity, Cancer therapy, Classic antifolates, Dihydrofolate reductase, Folyl polyglutamate synthetase, Chemical synthesis, Leukemia, Methotrexate, Multitarget antifolate, Non-classic antifolates, Polyglutamates, Thymidylate synthase, Tumor resistance, 2-(2-4-[(2, 4-diamino-pteridin-6-ylmethyl)-amino]-phenyl-2-oxo-ethyl) pentanedioic acid, 2-(2-4-[(2, 4-diamino-pteridin-6-ylmethyl)-methyl-amino]-phenyl-2-oxo-ethyl) pentanedioic acid

Abstract: A novel process for the preparation of two ketomethylenic antifolates, 2-(2-{4-[(2,4-diamino-pteridin-6-ylmethyl)-amino]- phenyl}-2-oxo-ethyl) pentanedioic acid and 2-(2-{4-[(2,4-diamino-pteridin-6-ylmethyl)-methyl-amino]-phenyl}-2-oxo-ethyl) pentanedioic acid is described herein. Both compounds were compared with methotrexate as inhibitors of human dihydrofolate reductase and thymidylate synthase. The in-vitro and in-vivo results suggest that these novel antifolate inhibitors could potentially constitute effective therapeutic molecules in the treatment of certain cancers and might present a lower toxicity profile than methotrexate.

Cite this article as:

F. Stoicescu Dan and Rotaru Maria, Synthesis and Biological Evaluation of Novel Antifolate Analogs as Potential Anticancer Treatment, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (2) . https://dx.doi.org/10.2174/1871520611313020022