Syntheses and evaluation of new acridone derivatives for selective binding of oncogene c-<i>myc</i> promoter i-motifs in gene transcriptional regulation

Shu, Bing; Cao, Jiaojiao; Kuang, Guotao; Qiu, Jun; Zhang, Meiling; Zhang, Yan; Wang, Mingxue; Li, Xiaoya; Kang, Shuangshuang; Ou, Tian‐Miao; Tan, Jia‐Heng; Huang, Zhi‐Shu; Li, Ding

doi:10.1039/c8cc00328a

Cited by 48 publications

(31 citation statements)

References 24 publications

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“…Recently, PBP1 and acridone derivatives have been developed as i‐motif binders, and shown to regulate the transcriptional activities of bcl‐2 and c‐myc genes, respectively. However, despite the growing number of reports on i‐motif‐interacting agents, so far, there is little structural information available on complexes between ligands and the i‐motif …”

Section: Methodsmentioning

confidence: 99%

Analysis of Interactions between Telomeric i‐Motif DNA and a Cyclic Tetraoxazole Compound

Masoud

Yamaoki

et al. 2018

ChemBioChem

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Section: Methodsmentioning

confidence: 99%

Analysis of Interactions between Telomeric i‐Motif DNA and a Cyclic Tetraoxazole Compound

Masoud

Yamaoki

et al. 2018

ChemBioChem

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“…Recently, Shu et al. developed a series of acridone derivatives and determined that one of these derivatives, B19, is capable of binding to and stabilizing the i-motif formed in the c-MYC promoter resulting in downregulation of gene expression and eventually to tumor cell death ( 89 ). The characterization of more i-motif structures at high resolution as well as its stabilization at neutral pH will contribute to increase the number of ligands that stabilize i-motifs.…”

Section: Biological Relevance Of I-motif Structuresmentioning

confidence: 99%

i-Motif DNA: structural features and significance to cell biology

Assi

Garavís

González

et al. 2018

Nucleic Acids Research

327

292

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The i-motif represents a paradigmatic example of the wide structural versatility of nucleic acids. In remarkable contrast to duplex DNA, i-motifs are four-stranded DNA structures held together by hemi- protonated and intercalated cytosine base pairs (C:C+). First observed 25 years ago, and considered by many as a mere structural oddity, interest in and discussion on the biological role of i-motifs have grown dramatically in recent years. In this review we focus on structural aspects of i-motif formation, the factors leading to its stabilization and recent studies describing the possible role of i-motifs in fundamental biological processes.

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“…Recently, it has been further demonstrated that i-motif structures can form in promoters and telomeric regions by using i-motif specific antibodies ( 19 ). We have also revealed that an acridone derivative could selectively bind to oncogene C-MYC promoter i-motif and down-regulate gene transcription and translation ( 26 ).…”

Section: Introductionmentioning

confidence: 99%

Upregulation of BCL-2 by acridone derivative through gene promoter i-motif for alleviating liver damage of NAFLD/NASH

Wang

Gong

et al. 2020

Nucleic Acids Research

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Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) are global epidemic public health problems with pathogenesis incompletely understood. Hepatocyte excessive apoptosis is a significant symbol for NAFLD/NASH patients, and therefore anti-apoptosis therapy could be used for NAFLD/NASH treatment. Up-regulation of BCL-2 has been found to be closely related with anti-apoptosis. BCL-2 gene promoter region has a C-rich sequence, which can form i-motif structure and play important role in regulating gene transcription. In this study, after extensive screening and evaluation, we found that acridone derivative A22 could up-regulate BCL-2 transcription and translation in vitro and in cells through selective binding to and stabilizing BCL-2 gene promoter i-motif. Our further experiments showed that A22 could reduce hepatocyte apoptosis in NAFLD/NASH model possibly through up-regulating BCL-2 expression. A22 could reduce inflammation, endoplasmic reticulum stress and cirrhosis in high-fat diet-fed mice liver model. Our findings provide a potentially new approach of anti-apoptosis for NAFLD/NASH treatment, and A22 could be further developed as a lead compound for NAFLD/NASH therapy. Our present study first demonstrated that gene promoter i-motif could be targeted for gene up-regulation for extended treatment of other important diseases besides cancer.

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Syntheses and evaluation of new acridone derivatives for selective binding of oncogene c-myc promoter i-motifs in gene transcriptional regulation

Cited by 48 publications

References 24 publications

Analysis of Interactions between Telomeric i‐Motif DNA and a Cyclic Tetraoxazole Compound

Analysis of Interactions between Telomeric i‐Motif DNA and a Cyclic Tetraoxazole Compound

i-Motif DNA: structural features and significance to cell biology

Upregulation of BCL-2 by acridone derivative through gene promoter i-motif for alleviating liver damage of NAFLD/NASH

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