期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/ijms22020749
关键词
1; 10-phenanthroline; guanyl hydrazones; human telomeric quadruplex; DNA interactions; antitumor agents
资金
- Spanish MINECO
- Spanish MICINN (AEI, Agencia Estatal de Investigacion) [CTQ2015-72625-EXP, PID2019-108251RB-I00]
- Spanish MICINN (Factoria de Cristalizacion) [RED2018-102574-T]
- Universidad de Alcala [CCG19/CC-009, CCG2018/EXP-024, UAH-AE-2017-2]
- Consejeria de Educacion [PEJ-2017-AI/SAL-6160, PEJ-2018-TL/SAL-11409]
- Juventud y Deporte de la Comunidad de Madrid [PEJ-2017-AI/SAL-6160, PEJ-2018-TL/SAL-11409]
- Fondo Social Europeo [PEJ-2017-AI/SAL-6160, PEJ-2018-TL/SAL-11409]
The novel quadruplex ligand PhenQE8 can efficiently recognize the hybrid quadruplex structures of human telomeric DNA, showing high binding affinity and quadruplex/duplex selectivity, and exhibit significant cytotoxic activity against tumor cells while having lower cytotoxicity in healthy human cells.
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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