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Additional file 1: Figure S1. 1H-NMR spectrum of CPT-SS-OH in DMSO-d6. Figure S2. 13C-NMR spectrum of CPT-SS-OH in DMSO-d6. Figure S3. 1H-NMR spectrum of CPT-SS-LG in CDCl3. Figure S4. 13C-NMR spectrum of CPT-SS-LG in CDCl3. Figure S5. 1H-NMR spectrum of IR820-NH2 in CD3OD. Figure S6. 13C-NMR spectrum of IR820-NH2 in CD3OD. Figure S7. 1H-NMR spectrum of IR820-SS-CPT in DMSO-d6. Figure S8. 13C-NMR spectrum of IR820-SS-CPT in DMSO-d6. Figure S9. ESI���MS spectrum of IR820-SS-CPT. Figure S10. 1H-NMR spectrum of CPT-CC-OH in CDCl3. Figure S11. 1H-NMR spectrum of CPT-CC-LG in CDCl3. Figure S12. 1H-NMR spectrum of IR820-CC-CPT in CD3OD. Figure S13. ESI���MS spectrum of IR820-CC-CPT. Figure S14. UV���vis���NIR absorbance spectra of IR820, IR820-SS-CPT, and CPT in methanol. Figure S15. Stability of the hydrodynamic particle size of the IR820-SS-CPT NPs. Figure S16. Fluorescence spectra of IR820-SS-CPT NPs (10 ��M) incubated with or without 10 mM GSH for 2 h in PBS. Figure S17. Relative fluorescent intensity of IR820-SS-CPT NPs internalized by 4T1 cells treated with PBS, chlorpromazine, nystatin, amiloride at 37 ��C, and PBS at 4 ��C using flow cytometry analysis. Figure S18. Relative viability of LO2 cells treated with various concentrations of CPT and IR820-SS-CPT NPs for 36 h. Error bars indicate SD (n = 3). Figure S19. In vivo pharmacokinetics profiles of IR820-SS-CPT NPs and free CPT in Sprague���Dawley (SD) rats. Error bars indicate SD (n = 3). Figure S20. Representative H&E staining of the major organs and tumors of the mice treated with PBS and IR820-SS-CPT NPs + NIR.

Scutellaria barbata D. Don has been used as a traditional Chinese medicine for antitumor and anti-inflammatory. However, there were just a few investigations about S. barbata D. Don according to bioactivity-directed isolation and online identification for the chemical constituents. In this work, eight compounds were isolated from S. barbata D. Don. The three flavonoids indicated the cytotoxic activity against human leukemic Reh cell lines. In addition, the constituents of S. barbata D. Don were further characterized and identified by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). The UHPLC- Q-TOF-MS method was in negative ion mode. HPLC separation was performed on a Tosoh TSK gel ODS-100V (4.6 × 150 mm, 3.0 μm) column by gradient elution using water containing 0.3% formic acid and acetonitrile as mobile phase at a flow rate of 0.8 mL min−1. A total of 18 compounds, including 4 phenolic acids and 14 flavonoids were tentatively characterize...

The use of metal complexes in the pharmaceutical industry has recently increased and as a result, novel metal‑based complexes have initiated an interest as potential anticancer agents. Copper (Cu), which is an essential trace element in all living organisms, is important in maintaining the function of numerous proteins and enzymes. It has recently been demonstrated that Cu complexes may be used as tumor‑specific proteasome inhibitors and apoptosis inducers, by targeting the ubiquitin‑proteasome pathway (UPP). Cu complexes have demonstrated promising results in preclinical studies. The UPP is important in controlling the expression, activity and location of various proteins. Therefore, selective proteasome inhibition and apoptotic induction in cancer cells have been regarded as potential anticancer strategies. The present short review discusses recent progress in the development of Cu complexes, including clioquinol, dithiocarbamates and Schiff bases, as proteasome inhibitors for cancer treatment. A discussion of recent research regarding the understanding of metal inhibitors based on Cu and ligand platforms is presented.

Metal-containing compounds have been extensively studied for many years as potent proteasome inhibitors. The 20S proteasome, the main component of the ubiquitin proteasome pathway, is one of the excellent targets in anticancer drug development. We recently reported that several copper complexes were able to inhibit cancer-special proteasome and induce cell death in human cancer cells. However, the involved molecular mechanism is not known yet. We therefore synthesized three copper complexes and investigated their abilities on inhibiting proteasome activity and inducting apoptosis in human breast cancer cells. Furthermore, we employed molecular dockings to analyze the possible interaction between the synthetic copper complexes and the β5 subunit of proteasome which only reflects the chymotrypsin-like activity. Our results demonstrate that three Cu(II) complexes possess potent proteasome inhibition capability in a dose-dependent and time-dependent manner in MDA-MB-231 human breast cancer cells. They could bind to the β5 subunit of the 20S proteasome, which consequently cause deactivation of the proteasome and tumor cell death. The present study is significant for providing important theoretical basis for design and synthesis of anticancer drugs with low toxicity, high efficiency and high selectivity.