Back to Search
Start Over
New antiglioma zwitterionic pronucleotides with an FdUMP framework.
- Source :
-
European journal of medicinal chemistry [Eur J Med Chem] 2018 Jan 20; Vol. 144, pp. 682-691. Date of Electronic Publication: 2017 Dec 21. - Publication Year :
- 2018
-
Abstract
- We have designed and synthesized new 5-fluoro-2'-deoxyuridine 5'-phosphate pronucleotides which can function as potential agents against the glioblastoma multiforme tumor. Their anti-malignant potency has been tested against T98G, U-118 MG, U-87 MG gliomas, HeLa, and Caco-2 cancer cell lines, using MRC-5 healthy cells as a reference. Five of the sixteen compounds (4c, 4f-i) exhibited significant anticancer potency and high selectivity indices (SI 12-66). It is likely that these zwitterionic pronucleotides may function in a similar manner to zwitterionic phospholipids, by inducing cell membrane charge disorder, making the cell permeable to bioactive agents. The most promising therapeutic pronucleotides 4c, 4f-h, have high intestinal-blood uptake potency (Caco-2 cell line), and may be considered as potential, orally administrated, anticancer drugs.<br /> (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)
- Subjects :
- Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Cell Proliferation drug effects
Cell Survival drug effects
Cytidine Monophosphate chemistry
Cytidine Monophosphate pharmacology
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Glioblastoma pathology
Humans
Molecular Structure
Nucleotides chemical synthesis
Nucleotides chemistry
Structure-Activity Relationship
Tumor Cells, Cultured
Antineoplastic Agents pharmacology
Cytidine Monophosphate analogs & derivatives
Glioblastoma drug therapy
Nucleotides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1768-3254
- Volume :
- 144
- Database :
- MEDLINE
- Journal :
- European journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 29289891
- Full Text :
- https://doi.org/10.1016/j.ejmech.2017.12.070