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Macrocyclic biphenyl tetraoxazoles: synthesis, evaluation as G-quadruplex stabilizers and cytotoxic activity.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2013 Aug 01; Vol. 21 (15), pp. 4511-20. Date of Electronic Publication: 2013 May 30. - Publication Year :
- 2013
-
Abstract
- A series of macrocyclic biphenyl tetraoxazoles was synthesized. The latter stages of the synthetic approach allowed for the addition of varied N-protected α-amino acids, which were subsequently deprotected and condensed to provide the desired macrocycles. Improved yields could be realized in the macrocyclization step of their synthesis relative to other macrocyclic G-quadruplex stabilizers. These 24-membered macrocycles were evaluated for their ability to stabilize G-quadruplex DNA and for their relative cytotoxicity against human tumor cells. These biphenyl tetraoxazoles were not strong ligands for G-quadruplex DNA relative to other macrocyclic polyoxazoles. This reduced stabilizing potential did correlate with their comparatively lower cytotoxic activity as observed in the human tumor cell lines, RPMI 8402 and KB3-1. These studies provide useful insights into the conformational requirements for the development of selective and more potent G-quadruplex ligands.<br /> (Copyright © 2013. Published by Elsevier Ltd.)
- Subjects :
- Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacology
Biphenyl Compounds chemical synthesis
Biphenyl Compounds chemistry
Biphenyl Compounds pharmacology
Cell Line, Tumor
Humans
Macrocyclic Compounds chemical synthesis
Models, Molecular
Molecular Structure
Oxazoles chemical synthesis
G-Quadruplexes drug effects
Macrocyclic Compounds pharmacology
Oxazoles chemistry
Oxazoles pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 21
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 23787291
- Full Text :
- https://doi.org/10.1016/j.bmc.2013.05.033