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dc.contributor.authorKhungar, Bharti-
dc.date.accessioned2024-09-11T06:54:10Z-
dc.date.available2024-09-11T06:54:10Z-
dc.date.issued2022-
dc.identifier.urihttps://www.mdpi.com/1420-3049/27/9/2672-
dc.identifier.urihttp://dspace.bits-pilani.ac.in:8080/jspui/xmlui/handle/123456789/15526-
dc.description.abstractHuman 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.isoenen_US
dc.publisherMDPIen_US
dc.subjectChemistryen_US
dc.subjectAPE/Ref-1en_US
dc.subjectHuman melanomaen_US
dc.subjectSmall molecular inhibitorsen_US
dc.subjectReactive oxygen species (ROS)en_US
dc.titleBis-Cinnamamide Derivatives as APE/Ref-1 Inhibitors for the Treatment of Human Melanomaen_US
dc.typeArticleen_US
Appears in Collections:Department of Chemistry

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