A Transformable Specific-Responsive Peptide for One-Step Synergistic Therapy of Bladder Cancer.

Synergistic therapy has shown greater advantages compared with monotherapy. However, the complex multiple-administration plan and potential side effects limit its clinical application. A transformable specific-responsive peptide (TSRP) is utilized to one-step achieve synergistic therapy integrating anti-tumor, anti-angiogenesis and immune response. The TSRP is composed of: i) Recognition unit could specifically target and inhibit the biological function of FGFR-1; ii) Transformable unit could self-assembly and trigger nanofibers formation; iii) Reactive unit could specifically cleaved by MMP-2/9 in tumor micro-environment; iv) Immune unit, stimulate the release of immune cells when LTX-315 (Immune-associated oncolytic peptide) exposed. Once its binding to FGFR-1, the TSRP could cleaved by MMP-2/9 to form the nanofibers on the cell membrane, with a retention time of up to 12 h. Through suppressing the phosphorylation levels of ERK 1/2 and PI3K/AKT signaling pathways downstream of FGFR-1, the TSRP significant inhibit the growth of tumor cells and the formation of angioginesis. Furthermore, LTX-315 is exposed after TSRP cleavage, resulting in Calreticulin activation and CD8+ T cells infiltration. All above processes together contribute to the increasing survival rate of tumor-bearing mice by nearly 4-folds. This work presented a unique design for the biological application of one-step synergistic therapy of bladder cancer.

Rhodium(III)-Catalyzed Direct Coupling of Quinoline-8-Carbaldehydes with (Het)Arylboronic Acids for the Synthesis of 8-Aryloylquinolines.

Herein, we describe a method for the synthesis of aryl-(het)aryl ketones by Rh(III)-catalyzed direct coupling between quinoline-8-carbaldehydes and (het)arylboronic acids. The method has a broad substrate scope, a high functional group tolerance, and uses commercially available starting materials. Scale-up of the reaction and subsequent synthesis of tubulin polymerization inhibitor demonstrated its utilities. A plausible mechanism was proposed on the basis of the fact that a stable cycloacylrhodium intermediate complex could be used as catalyst, and the complex reacted stoichiometrically with (het)arylboronic acids.

Dehydrogenation of N-Heterocycles by Superoxide Ion Generated through Single-Electron Transfer.

Nitrogen-containing heteroarene motifs are found in numerous pharmaceuticals, natural products, and synthetic materials. Although several elegant methods for synthesis of these compounds through dehydrogenation of the corresponding saturated heterocycles have been reported, some of the methods are hampered by long reaction times, harsh conditions, and the need for catalysts that are not readily available. This work reports a novel method for dehydrogenation of N-heterocycles. Specifically, O2.- generated in situ acts as the oxidant for N-heterocycle substrates that are susceptible to oxidation through a hydrogen atom transfer mechanism. This method provides a general, green route to N-heteroarenes.

Design, synthesis, anti-TMV, fungicidal, and insecticidal activity evaluation of 1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid derivatives based on virus inhibitors of plant sources.

By drawing the creation ideas of botanical pesticides, a series of tetrahydro-ß-carboline-3-carboxylic acid derivatives were designed and synthesized, and first evaluated for their anti-TMV, fungicidal and insecticidal activities. Most of these derivatives exhibited good antiviral activity against TMV both in vitro and in vivo. Especially, the activities of compounds 8 and 15 in vivo were higher than that of ribavirin. The compound 8 exhibited more than 70% fungicidal activities against Cercospora arachidicola Hori, Alternaria solani, Bipolaris maydis, and Rhizoctonia solani at 50mg/kg, compounds 16 and 20 exhibited more than 60% insecticidal activities against Mythimna separate and Ostrinia nubilalis.

Blue light photoredox-catalysed acetalation of alkynyl bromides.

Herein, we report an organo-photoredox-based protocol using 2,2-diethoxyacetic acid as the acetal source to achieve acetalation of alkynyl bromides to afford various alkynyl acetal products. In addition to arylethynyl bromides, substrates bearing heteroaryl rings (thiophene, pyridine, and indole) smoothly gave the corresponding acetalation products. This mild protocol has potential utility for the synthesis of aldehydes by further protonization.

Visible-Light-Induced Copper-Catalyzed Decarboxylative Coupling of Redox-Active Esters with N-Heteroarenes.

Herein we report a protocol for visible-light-induced copper-catalyzed decarboxylative coupling reactions between N-heteroarenes and redox-active esters. Various N-hydroxyphthalimide esters reacted with isoquinoline, quinoline, pyridine, pyrimidine, quinazoline, phthalazine, phenanthridine, and pyridazine to give the corresponding products in modest to excellent yields. The reactions proceed under mild conditions and have a broad scope and high functional group tolerance. Mechanistic studies revealed that the catalytic behavior of CuI photocatalyst generated in situ was consistent with that of preformed [Cu(dmp)(xantphos)]BF4.