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DC Field | Value | Language |
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dc.contributor.author | Khungar, Bharti | - |
dc.date.accessioned | 2024-09-11T06:54:10Z | - |
dc.date.available | 2024-09-11T06:54:10Z | - |
dc.date.issued | 2022 | - |
dc.identifier.uri | https://www.mdpi.com/1420-3049/27/9/2672 | - |
dc.identifier.uri | http://dspace.bits-pilani.ac.in:8080/jspui/xmlui/handle/123456789/15526 | - |
dc.description.abstract | Human malignant melanoma exhibits imbalances in redox status, leading to activation of many redox-sensitive signaling pathways. APE/Ref-1 is a multifunctional protein that serves as a redox chaperone that regulates many nuclear transcription factors and is an important mechanism in cancer cell survival of oxidative stress. Previous studies showed that APE/Ref-1 is a potential druggable target for melanoma therapy. In this study, we synthesized a novel APE/Ref-1 inhibitor, bis-cinnamoyl-1,12-dodecamethylenediamine (2). In a xenograft mouse model, compound 2 treatment (5 mg/kg) significantly inhibited tumor growth compared to the control group, with no significant systemic toxicity observed. We further synthesized compound 2 analogs to determine the structure-activity relationship based on their anti-melanoma activities. Among those, 4-hydroxyphenyl derivative (11) exhibited potent anti-melanoma activities and improved water solubility compared to its parental compound 2. The IC50 of compound 11 was found to be less than 0.1 μM. Compared to other known APE/Ref-1 inhibitors, compound 11 exhibited increased potency in inhibiting melanoma proliferation. As determined by luciferase reporter analyses, compound 2 was shown to effectively inhibit H2O2-activated AP-1 transcription activities. Targeting APE/Ref-1-mediated signaling using pharmaceutical inhibitors is a novel and effective strategy for melanoma treatment with potentially high impact. | en_US |
dc.language.iso | en | en_US |
dc.publisher | MDPI | en_US |
dc.subject | Chemistry | en_US |
dc.subject | APE/Ref-1 | en_US |
dc.subject | Human melanoma | en_US |
dc.subject | Small molecular inhibitors | en_US |
dc.subject | Reactive oxygen species (ROS) | en_US |
dc.title | Bis-Cinnamamide Derivatives as APE/Ref-1 Inhibitors for the Treatment of Human Melanoma | en_US |
dc.type | Article | en_US |
Appears in Collections: | Department of Chemistry |
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