12-N-Methylated 5,6-dihydrobenzo[c]acridine derivatives: A new class of highly selective ligands for c-myc G-quadruplex DNA
| Autor: | Lian-Quan Gu, Zhi-Shu Huang, Sheng-Rong Liao, Jia-Heng Tan, Tian-Miao Ou, Wei-Bin Wu, Chen-Xi Zhou, Ding Li |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Circular dichroism Transcription Genetic Molecular model Stereochemistry Antineoplastic Agents Ligands Nucleic Acid Denaturation G-quadruplex Methylation Substrate Specificity Proto-Oncogene Proteins c-myc chemistry.chemical_compound Transcription (biology) Cell Line Tumor Drug Discovery Humans Transition Temperature Surface plasmon resonance Cell Proliferation Pharmacology Base Sequence Organic Chemistry DNA General Medicine Reverse transcriptase G-Quadruplexes Förster resonance energy transfer chemistry Drug Design Acridines |
| Zdroj: | European Journal of Medicinal Chemistry. 53:52-63 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2012.03.034 |
| Popis: | 12-N-Methylated and non-methylated 5,6-dihydrobenzo[c]acridine derivatives were designed and synthesized as new series of c-myc G-quadruplex binding ligands. Their interactions with c-myc G-quadruplex were evaluated using fluorescence resonance energy transfer (FRET) melting assay, circular dichroism (CD) spectroscopy, surface plasmon resonance (SPR), polymerase chain reaction (PCR) stop assay, and molecular modeling. Compared with the non-methylated derivatives, 12-N-methylated derivatives had stronger binding affinity and stabilizing ability to c-myc G-quadruplex structure, and could more effectively stack on the G-quartet surface. All these derivatives had high selectivity for c-myc G-quadruplex DNA over duplex DNA. The reverse transcription (RT) PCR assay showed that compound 21c could down-regulate transcription of c-myc gene in Ramos cell line containing NHE III(1) element, but had no effect in CA46 cell line with NHE III(1) element removed. |
| Databáze: | OpenAIRE |
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