Cobalt-Catalyzed Addition of Azoles to Alkynes

A ternary catalytic system consisting of a cobalt salt, a diphosphine ligand, and a Grignard reagent promotes syn-addition of an azole C(2)−H bond across an unactivated internal alkyne with high chemo-, regio-, and stereoselectivities under mild conditions. Mechanistic experiments suggest that the reaction involves oxidative addition of the oxazolyl C−H bond to the cobalt center, alkyne insertion into the Co−H bond, and reductive elimination of the resulting diorganocobalt species

Synthesis of Oxazolidines and Dihydroxazines via Cyclization of α‑Aminated Ketones

A new approach to oxazolidines and dihydroxazines was developed by regioselective cyclization of α-aminated ketones under transition metal-free conditions. Oxazolidine derivatives were generated in the presence of chloro benziodoxole and TFA, while dihydroxazines were formed without a hypervalent iodine reagent. The reaction was performed under room temperature and gave the products in good to excellent yields

ZnCl₂‑Catalyzed [3 + 2] Cycloaddition of Benzimidates and 2<i>H</i>‑Azirines for the Synthesis of Imidazoles

ZnCl2-catalyzed [3 + 2] cycloaddition reaction of benzimidates and 2H-azirines has been developed. This convenient method allowed the efficient construction of a series of multisubstituted imidazoles in moderate to good yields under mild reaction conditions. This transformation exhibits good reactivity and high functional group tolerance

α‑Palladation of Imines as Entry to Dehydrogenative Heck Reaction: Aerobic Oxidative Cyclization of <i>N</i>‑Allylimines to Pyrroles

We report here a palladium(II)-catalyzed oxidative cyclization reaction of <i>N</i>-allylimines derived from methyl ketones, typically acetophenones, affording pyrrole derivatives at room temperature under oxygen atmosphere. The reaction likely proceeds through α-palladation of the imine followed by olefin migratory insertion and β-hydride elimination, thus representing a new example of aerobic dehydrogenative Heck cyclization

Image2_Targeting MALT1 Suppresses the Malignant Progression of Colorectal Cancer via miR-375/miR-365a-3p/NF-κB Axis.TIFF

Colorectal cancer (CRC) is a malignant tumor with the second highest morbidity and the third highest mortality in the world, while the therapeutic options of targeted agents remain limited. Here, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), known as the upstream of the NF-κB signaling pathway, was identified to be highly upregulated in CRC tumors and cell lines. Furthermore, the downregulation of MALT1 or inhibition of its proteolytic function by MI-2 suppressed the cell proliferation and migration of CRC cells. In vivo, suppressing the MALT1 expression or its proteasome activity effectively reduced the size of the subcutaneous tumor in nude mice. Mechanistically, miR-375 and miR-365a-3p were identified to inhibit NF-κB activation via targeting MALT1. Overall, our results highlight that a novel regulatory axis, miRNA-MALT1-NF-κB, plays a vital role in the progression of CRC and provides novel and hopeful therapeutic targets for clinical treatment.</p

Image3_Targeting MALT1 Suppresses the Malignant Progression of Colorectal Cancer via miR-375/miR-365a-3p/NF-κB Axis.TIFF

Colorectal cancer (CRC) is a malignant tumor with the second highest morbidity and the third highest mortality in the world, while the therapeutic options of targeted agents remain limited. Here, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), known as the upstream of the NF-κB signaling pathway, was identified to be highly upregulated in CRC tumors and cell lines. Furthermore, the downregulation of MALT1 or inhibition of its proteolytic function by MI-2 suppressed the cell proliferation and migration of CRC cells. In vivo, suppressing the MALT1 expression or its proteasome activity effectively reduced the size of the subcutaneous tumor in nude mice. Mechanistically, miR-375 and miR-365a-3p were identified to inhibit NF-κB activation via targeting MALT1. Overall, our results highlight that a novel regulatory axis, miRNA-MALT1-NF-κB, plays a vital role in the progression of CRC and provides novel and hopeful therapeutic targets for clinical treatment.</p

Table2_Targeting MALT1 Suppresses the Malignant Progression of Colorectal Cancer via miR-375/miR-365a-3p/NF-κB Axis.XLSX

Colorectal cancer (CRC) is a malignant tumor with the second highest morbidity and the third highest mortality in the world, while the therapeutic options of targeted agents remain limited. Here, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), known as the upstream of the NF-κB signaling pathway, was identified to be highly upregulated in CRC tumors and cell lines. Furthermore, the downregulation of MALT1 or inhibition of its proteolytic function by MI-2 suppressed the cell proliferation and migration of CRC cells. In vivo, suppressing the MALT1 expression or its proteasome activity effectively reduced the size of the subcutaneous tumor in nude mice. Mechanistically, miR-375 and miR-365a-3p were identified to inhibit NF-κB activation via targeting MALT1. Overall, our results highlight that a novel regulatory axis, miRNA-MALT1-NF-κB, plays a vital role in the progression of CRC and provides novel and hopeful therapeutic targets for clinical treatment.</p

AntagomiR-365 inhibits tumorgenesis and restores NFIB expression both <i>in vitro</i> and <i>in vivo</i>.

<p>(A) The expression of NFIB, p53, CDK6 and Bcl-2 proteins in CSCC cells transfected with antagomiR NC and antagomiR-365 was detected by western blot using GAPDH as a loading control. A representative result is shown here. (B) A representative picture shows the change in tumor volume in xenograft model of BALB/c-nu mice after antagomir-365 treatment 3 weeks with intratumoural injection. The right back flank of BALB/c-nu mice was injected subcutaneously with A431 cells <i>in vivo</i> with a volume of more than 150 mm³ (n = 5) in comparison with PBS treatment (n = 5). Red arrow head shows the tumor formation from representative mice 21 days after treatment (controls were treated with PBS). (C) Tumor volumes (mm³) were recorded in time points as indicated in the growth curve. Relative tumor volumes are shown with respect to day 7. Data are plotted as mean ± S.E. (D) AntagomiR-365 injection drastically decreased the expression levels of the miR-365 in xenografts and thus led to the up-regulation of NFIB and p53 and down-regulation of CDK6 and Bcl-2. Each bar represents the average expression from 5 individual xenografts. Data are plotted as mean ± S.E. (E) IHC staining of NFIB, p53, CDK6 and Bcl-2 on sections of xenograft tumors. Representative fields are shown here and index of positive signal was calculated (n = 10).</p

Image1_Targeting MALT1 Suppresses the Malignant Progression of Colorectal Cancer via miR-375/miR-365a-3p/NF-κB Axis.TIFF

Colorectal cancer (CRC) is a malignant tumor with the second highest morbidity and the third highest mortality in the world, while the therapeutic options of targeted agents remain limited. Here, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), known as the upstream of the NF-κB signaling pathway, was identified to be highly upregulated in CRC tumors and cell lines. Furthermore, the downregulation of MALT1 or inhibition of its proteolytic function by MI-2 suppressed the cell proliferation and migration of CRC cells. In vivo, suppressing the MALT1 expression or its proteasome activity effectively reduced the size of the subcutaneous tumor in nude mice. Mechanistically, miR-375 and miR-365a-3p were identified to inhibit NF-κB activation via targeting MALT1. Overall, our results highlight that a novel regulatory axis, miRNA-MALT1-NF-κB, plays a vital role in the progression of CRC and provides novel and hopeful therapeutic targets for clinical treatment.</p