Design, synthesis and SAR of novel 7-azaindole derivatives as potential Erk5 kinase inhibitor with anticancer activity.

The extracellular signal-regulated kinase 5 (Erk5) signaling plays a crucial role in cancer, and regulating its activity may have potential in cancer chemotherapy. In this study, a series of novel 7-azaindole derivatives (4a-5o) were designed and synthesized. Their antitumor activities on human lung cancer A549 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 4',6-diamidino-2-phenylindole (DAPI) staining and colony formation assay. Among them, compounds 4a, 4 h, 5d and 5j exhibited good anti-proliferative activity with the IC50 values of 6.23 µg/mL, 8.52 µg/mL, 7.33 µg/mL and 4.56 µg/mL, respectively, equivalent to Erk5 positive control XMD8-92 (IC50 = 5.36 µg/mL). The results of structure-activity relationships (SAR) showed that double bond on the piperidine ring and N atoms at the N7 position of 7-azaindole was essential for their antiproliferative activity. Furthermore, compounds 4a and 5j exhibited good inhibition on Erk5 kinase through Western blot analysis and possible action site of compounds with Erk5 kinase was elucidated by molecular docking.

Electrochemical treatment of malachite green dye wastewater by pulse three-dimensional electrode method.

Water pollution is becoming more and more serious nowadays, and water resources are in shortage. As an environmentally friendly wastewater treatment technology without secondary pollution, the three-dimensional electrode method has received more and more attention. However, the conventional direct current (DC) three-dimensional electrode method has the disadvantages of high energy consumption and low current efficiency. Based on this, this work investigated the treatment of malachite green (MG) dye wastewater by pulse three-dimensional electrode method. The influences of pulse duty cycle, pulse period, electrolysis voltage, initial pH, aeration rate and Na2SO4 concentration on MG degradation were investigated. The results showed that under the optimal operating conditions of pulse duty cycle of 0.4, pulse period of 15 s, electrolysis voltage of 15 V, initial pH of 5, aeration rate of 0.5 L/min, Na2SO4 concentration of 0.10 mol/L, the removal rates of MG and COD reached 96.2% and 80.5%, respectively, the current efficiency reached 93.4%, and the energy consumption was 24.2 kWh/kg COD after 150 min. Compared with DC power supply mode, the MG removal rate, COD removal rate and current efficiency were enhanced, and the energy consumption was reduced by 83.9%. Moreover, the generation capacity of ·OH was increased under pulse power supply mode. Finally, a possible degradation pathway of MG in pulse power supply mode was inferred using UV-vis and GC-MS analysis. This study indicates that the pulse three-dimensional electrode method is an efficient and low-energy-consumption wastewater treatment method with stable degradation performance for MG dye wastewater.

Novel pH-Triggered Doxorubicin-Releasing Nanoparticles Self-Assembled by Functionalized ß-Cyclodextrin and Amphiphilic Phthalocyanine for Anticancer Therapy.

Cyclodextrins (CDs), as pharmaceutical excipients with excellent biocompatibility, non-immunogenicity, and low toxicity in vivo, are widely used to carry drugs by forming inclusion complexes for improving the solubility and stability of drugs. However, the limited space of CDs' lipophilic central cavity affects the loading of many drugs, especially with larger molecules. In this study, ß-CDs were modified by acetonization to improve the affinity for the chemotherapy drug doxorubicin (DOX), and doxorubicin-adsorbing acetalated ß-CDs (Ac-CD:DOX) self-assembled to nanoparticles, followed by coating with the amphiphilic zinc phthalocyanine photosensitizer ZnPc-(PEG)5 for antitumor therapy. The final product ZnPc-(PEG)5:Ac-CD:DOX was demonstrated to have excellent stability and pH-sensitive drug release characteristics. The cell viability and apoptosis assay showed synergistic cytotoxic effects of chemotherapy and phototherapy. The mechanism of cytotoxicity was analyzed in terms of intracellular reactive oxygen species, mitochondrial membrane potential, and subcellular localization. More importantly, in vivo experiments indicated that ZnPc-(PEG)5:Ac-CD:DOX possessed significant tumor targeting, prominent antitumor activity, and less side effects. Our strategy expands the application of CDs as drug carriers and provides new insights into the development of CD chemistry.