Anti-Cancer Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Michelle Prudhomme  
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France

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

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

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.

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

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Article Details

VOLUME: 13
ISSUE: 2
Year: 2013
Page: [364 - 372]
Pages: 9
DOI: 10.2174/1871520611313020022
Price: $58