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

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

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 13 , Issue 2 , 2013

Become EABM
Become Reviewer
Call for Editor


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.

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

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2013
Page: [364 - 372]
Pages: 9
DOI: 10.2174/1871520611313020022
Price: $65

Article Metrics

PDF: 20