Binding characterization of anthraquinone derivatives by stabilizing G-quadruplex DNA leads to an anticancerous activity
G-quadruplex is a non-canonical secondary structure identified in the telomeric region and the promoter of many oncogenes. Anthraquinone derivatives, a well-known inducer of telomere disruption in malignant cells and activate the apoptotic pathway. We used biophysical and biochemical studies to conf...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253122003006 |
| _version_ | 1828293890934833152 |
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| author | Arpita Dey Kumud Pandav Mala Nath Ritu Barthwal Ramasare Prasad |
| author_facet | Arpita Dey Kumud Pandav Mala Nath Ritu Barthwal Ramasare Prasad |
| author_sort | Arpita Dey |
| collection | DOAJ |
| description | G-quadruplex is a non-canonical secondary structure identified in the telomeric region and the promoter of many oncogenes. Anthraquinone derivatives, a well-known inducer of telomere disruption in malignant cells and activate the apoptotic pathway. We used biophysical and biochemical studies to confirm the interaction of synthesized anthraquinone derivatives with the human telomeric G-quadruplex sequence. The binding affinity of N-2DEA and N-1DEA are Kb = 4.8 × 106 M−1 and Kb = 7.6 × 105 M−1, respectively, leading to hypochroism, fluorescence quenching with minor redshift and ellipticity variations indicating ligand binding in the external groove. We found that sodium ions induced stabilization more rather than potassium ions. Molecular docking of complex demonstrates a molecule’s exterior binding to a quadruplex. The investigation of ROS activity indicated that the cell initiates mortality in response to the IC50 concentration. Cellular morphology, nuclear condensation, and fragmentation were altered in the treated cell, impairing cellular function. Finally, the transcriptional regulatory study paves the way for drug design as an anti-cancer agent because of the tremendous possibilities of changing substituent groups on anthraquinones to improve efficacy and selectivity for G-quartet DNA. Our research focused on how ligand binding to telomere sequences induces oxidative stress and inhibits the growth of malignant cells. |
| first_indexed | 2024-04-13T11:29:01Z |
| format | Article |
| id | doaj.art-a8c7b28430004fff95aebe909636ce1f |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-04-13T11:29:01Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-a8c7b28430004fff95aebe909636ce1f2022-12-22T02:48:37ZengElsevierMolecular Therapy: Nucleic Acids2162-25312022-12-0130648662Binding characterization of anthraquinone derivatives by stabilizing G-quadruplex DNA leads to an anticancerous activityArpita Dey0Kumud Pandav1Mala Nath2Ritu Barthwal3Ramasare Prasad4Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, IndiaDepartment of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, IndiaDepartment of Chemistry, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, IndiaDepartment of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India; Corresponding author Ritu Barthwal, PhD, Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India.Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India; Corresponding author Ramasare Prasad, PhD, Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India.G-quadruplex is a non-canonical secondary structure identified in the telomeric region and the promoter of many oncogenes. Anthraquinone derivatives, a well-known inducer of telomere disruption in malignant cells and activate the apoptotic pathway. We used biophysical and biochemical studies to confirm the interaction of synthesized anthraquinone derivatives with the human telomeric G-quadruplex sequence. The binding affinity of N-2DEA and N-1DEA are Kb = 4.8 × 106 M−1 and Kb = 7.6 × 105 M−1, respectively, leading to hypochroism, fluorescence quenching with minor redshift and ellipticity variations indicating ligand binding in the external groove. We found that sodium ions induced stabilization more rather than potassium ions. Molecular docking of complex demonstrates a molecule’s exterior binding to a quadruplex. The investigation of ROS activity indicated that the cell initiates mortality in response to the IC50 concentration. Cellular morphology, nuclear condensation, and fragmentation were altered in the treated cell, impairing cellular function. Finally, the transcriptional regulatory study paves the way for drug design as an anti-cancer agent because of the tremendous possibilities of changing substituent groups on anthraquinones to improve efficacy and selectivity for G-quartet DNA. Our research focused on how ligand binding to telomere sequences induces oxidative stress and inhibits the growth of malignant cells.http://www.sciencedirect.com/science/article/pii/S2162253122003006MT: Oligonucleotides: Therapies and applicationsG quadruplexsensogramanthraquinone derivativespectroscopic studygroove binding |
| spellingShingle | Arpita Dey Kumud Pandav Mala Nath Ritu Barthwal Ramasare Prasad Binding characterization of anthraquinone derivatives by stabilizing G-quadruplex DNA leads to an anticancerous activity Molecular Therapy: Nucleic Acids MT: Oligonucleotides: Therapies and applications G quadruplex sensogram anthraquinone derivative spectroscopic study groove binding |
| title | Binding characterization of anthraquinone derivatives by stabilizing G-quadruplex DNA leads to an anticancerous activity |
| title_full | Binding characterization of anthraquinone derivatives by stabilizing G-quadruplex DNA leads to an anticancerous activity |
| title_fullStr | Binding characterization of anthraquinone derivatives by stabilizing G-quadruplex DNA leads to an anticancerous activity |
| title_full_unstemmed | Binding characterization of anthraquinone derivatives by stabilizing G-quadruplex DNA leads to an anticancerous activity |
| title_short | Binding characterization of anthraquinone derivatives by stabilizing G-quadruplex DNA leads to an anticancerous activity |
| title_sort | binding characterization of anthraquinone derivatives by stabilizing g quadruplex dna leads to an anticancerous activity |
| topic | MT: Oligonucleotides: Therapies and applications G quadruplex sensogram anthraquinone derivative spectroscopic study groove binding |
| url | http://www.sciencedirect.com/science/article/pii/S2162253122003006 |
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