PhenQE8, a Novel Ligand of the Human Telomeric Quadruplex †
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Departamento de Química Orgánica y Química Inorgánica, Instituto de Investigación Química “Andrés M. del Río” (IQAR), Universidad de Alcalá, 28805 Alcalá de Henares, Madrid, Spain
*
Authors to whom correspondence should be addressed.
†
Dedicated to the memory of Prof. Dr. Carolina Burgos.
Int. J. Mol. Sci. 2021, 22(2), 749; https://doi.org/10.3390/ijms22020749
Received: 30 November 2020
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Revised: 30 December 2020
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Accepted: 10 January 2021
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Published: 13 January 2021
(This article belongs to the Special Issue The Polymorphic World of G-Quadruplexes: From Structural Insights to Functional Activity)
A novel quadruplex ligand based on 1,10-phenanthroline and incorporating two guanyl hydrazone functionalities, PhenQE8, is reported herein. Synthetic access was gained in a two-step procedure with an overall yield of 61%. X-ray diffraction studies revealed that PhenQE8 can adopt an extended conformation that may be optimal to favor recognition of quadruplex DNA. DNA interactions with polymorphic G-quadruplex telomeric structures were studied by different techniques, such as Fluorescence resonance energy transfer (FRET) DNA melting assays, circular dichroism and equilibrium dialysis. Our results reveal that the novel ligand PhenQE8 can efficiently recognize the hybrid quadruplex structures of the human telomeric DNA, with high binding affinity and quadruplex/duplex selectivity. Moreover, the compound shows significant cytotoxic activity against a selected panel of cultured tumor cells (PC-3, HeLa and MCF-7), whereas its cytotoxicity is considerably lower in healthy human cells (HFF-1 and RPWE-1).
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Keywords:
1,10-phenanthroline; guanyl hydrazones; human telomeric quadruplex; DNA interactions; antitumor agents
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MDPI and ACS Style
Gratal, P.B.; Quero, J.G.; Pérez-Redondo, A.; Gándara, Z.; Gude, L. PhenQE8, a Novel Ligand of the Human Telomeric Quadruplex. Int. J. Mol. Sci. 2021, 22, 749. https://doi.org/10.3390/ijms22020749
AMA Style
Gratal PB, Quero JG, Pérez-Redondo A, Gándara Z, Gude L. PhenQE8, a Novel Ligand of the Human Telomeric Quadruplex. International Journal of Molecular Sciences. 2021; 22(2):749. https://doi.org/10.3390/ijms22020749
Chicago/Turabian StyleGratal, Patricia B., Julia G. Quero, Adrián Pérez-Redondo, Zoila Gándara, and Lourdes Gude. 2021. "PhenQE8, a Novel Ligand of the Human Telomeric Quadruplex" International Journal of Molecular Sciences 22, no. 2: 749. https://doi.org/10.3390/ijms22020749
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