Bis-Cinnamamide Derivatives as APE/Ref-1 Inhibitors for the Treatment of Human Melanoma.

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.

Exploration of fluorescence behavior of an imidazolium-based chemosensor in solution and in the solid state and its turn-on response to Al3+ in pure aqueous medium.

An imidazolium-based quinoline Schiff base ImSB was developed and fully characterized by FT-IR, 1H and 13C NMR spectroscopy, mass spectrometry, and X-ray crystallography. The fluorescence behaviour of ImSB in solution and in the solid state, keto-enol stability at different concentrations and pH in aqueous medium were investigated. The UV-visible and fluorescence studies were performed to determine the response of ImSB towards different ions in aqueous medium. ImSB showed a turn-on fluorescence behaviour with high selectivity towards Al3+ over various cations and anions due to chelation-enhanced fluorescence (CHEF), inhibition of photoinduced electron transfer (PET) and restriction of C[double bond, length as m-dash]N isomerization. The low detection limit for Al3+ was 54 nM and Job's plot confirmed 1 : 1 stoichiometry between ImSB and Al3+ with a high binding constant value of 4.16 × 106 M-1. Monitoring of Al3+ was also demonstrated in real water samples (mineral, river and tap water). The structural and electronic parameters of ImSB and ImSB-Al3+ were also studied theoretically.

Copper-catalyzed tandem azide-alkyne cycloaddition, Ullmann type C-N coupling, and intramolecular direct arylation.

A ligand-free copper-catalyzed tandem azide-alkyne cycloaddition (CuAAC), Ullmann-type C-N coupling, and intramolecular direct arylation has been described. The designed strategy resulted in the synthesis of a novel trazole-fused azaheterocycle framework. The reaction gave good yields (59-77%) of 1,2,3-triazole-fused imidazo[1,2-a]pyridines in a single step.

One-pot sequential C-N coupling and cross dehydrogenative couplings: synthesis of novel azole fused imidazo[1,2-a]pyridines.

An efficient one-pot protocol has been developed using sequential C-N coupling and intramolecular dehydrogenative cross-couplings for the synthesis of azole fused imidazo[1,2-a]pyridine derivatives in good yields (62-78%).