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
Anti-Cancer Agents in Medicinal Chemistry
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.
Export Options
About this article
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
DOI https://dx.doi.org/10.2174/1871520611313020022 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Methylenetetrahydrofolate Reductase (MTHFR): A Novel Target for Cancer Therapy
Current Pharmaceutical Design Histone Deacetylase Inhibitors: Molecular and Biological Activity as a Premise to Clinical Application
Current Drug Metabolism The Role of Epigenetics in Drug Resistance in Cancer
Epigenetic Diagnosis & Therapy (Discontinued) WT1 Peptide Vaccine as a Paradigm for “Cancer Antigen-Derived Peptide”-Based Immunotherapy for Malignancies: Successful Induction of Anti-Cancer Effect by Vaccination with a Single Kind of WT1 Peptide
Anti-Cancer Agents in Medicinal Chemistry Progress in the Preclinical Discovery and Clinical Development of Class I and Dual Class I/IV Phosphoinositide 3-Kinase (PI3K) Inhibitors
Current Medicinal Chemistry Determination of Human Serum α1-Acid Glycoprotein and Albumin Binding of Various Marketed and Preclinical Kinase Inhibitors
Current Medicinal Chemistry Pulmonary Surfactant Proteins A and D: Innate Immune Functions and Biomarkers for Lung Diseases
Current Pharmaceutical Design Effect of Alpha-1-Acid Glycoprotein Binding on Pharmacokinetics and Pharmacodynamics
Current Drug Metabolism Development of Sendai Virus Vectors and their Potential Applications in Gene Therapy and Regenerative Medicine
Current Gene Therapy Nanoparticles for Tumor Targeted Therapies and Their Pharmacokinetics
Current Drug Metabolism Role of miR-193a in Cancer: Complexity and Factors Control the Pattern of its Expression
Current Cancer Drug Targets Nitric Oxide in Cancer Therapeutics: Interaction with Cytotoxic Chemotherapy
Current Pharmaceutical Design G and C Iterons and Strings in MicroRNAs Should be Important in Regulation of mRNAs<sup>†</sup>
MicroRNA Insulin-like Growth Factor: Current Concepts and New Developments in Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery Molecular Pathology of Sarcomas
Reviews on Recent Clinical Trials Oncolytic Viruses for Induction of Anti-Tumor Immunity
Current Pharmaceutical Biotechnology Leukotriene A4 Hydrolase as a Target for Cancer Prevention and Therapy
Current Cancer Drug Targets Toxic Epidermal Necrolysis and Antifolate Drugs in Cancer Chemotherapy
Current Drug Safety Anticarcinogenic Actions of Tributyrin, A Butyric Acid Prodrug
Current Drug Targets The mTOR/4E-BP1/eIF4E Signalling Pathway as a Source of Cancer Drug Targets
Current Medicinal Chemistry