Cu₂O-Catalyzed C(sp³)-H/C(sp³)-H Cross-Coupling Using TEMPO: Synthesis of 3-(2-Oxoalkyl)-3-hydroxyoxindoles

<div><p></p><p>A simple, convenient and efficient oxidative cross-coupling reaction of oxindoles with ketones toward a variety of 3-(2-oxoalkyl)-3-hydroxyoxindoles in moderate to excellent yields has been developed. This transformation proceeds<i>via</i> a tandem oxidative cross-coupling by using TEMPO in air as an environmentally benign oxidant. This methodology provides an alternative approach for the direct generation of all-carbon quaternary centers at the C3 position of oxindoles.</p></div

Dual Function of RGD-Modified VEGI-192 for Breast Cancer Treatment

Identification of endogenous angiogenesis inhibitors has led to development of an increasingly attractive strategy for cancer therapy and other angiogenesis-driven diseases. Vascular endothelial growth inhibitor (VEGI), a potent and relatively nontoxic endogenous angiogenesis inhibitor, has been intensively studied, and this work shed new light on developing promising anti-angiogenic strategies. It is well-documented that the RGD (Arg-Gly-Asp) motif exhibits high binding affinity to integrin α_vβ₃, which is abundantly expressed in cancer cells and specifically associated with angiogenesis on tumors. Here, we designed a fusion protein containing the special RGD-4C motif sequence and VEGI-192, aimed at offering more effective multiple targeting to tumor cells and tumor vasculature, and higher anti-angiogenic and antitumor efficacy. Functional tests demonstrated that the purified recombinant human RGD-VEGI-192 protein (rhRGD-VEGI-192) potently inhibited endothelial growth in vitro and suppressed neovascularization in chicken chorioallantoic membrane in vivo, to a higher degree as compared with rhVEGI-192 protein. More importantly, rhRGD-VEGI-192, but not rhVEGI-192 protein, could potentially target MDA-MB-435 breast tumor cells, significantly inhibiting growth of MDA-MB-435 cells in vitro, triggered apoptosis in MDA-MB-435 cells by activation of caspase-8 as well as caspase-3, which was mediated by activating the JNK signaling associated with upregulation of pro-apoptotic protein Puma, and consequently led to the observed significant antitumor effect in vivo against a human breast cancer xenograft. Our study indicated that the RGD-VEGI-192 fusion protein might represent a novel anti-angiogenic and antitumor strategy