We report aryne generation from 2-triazenylarylboronic acids using an activator such as Brønsted acids, Lewis acids, and solid acids. With the use of (±)-Camphorsulfonic acid [(±)-CSA], the aryne precursors provided cycloadducts with a range of arynophiles in high yields. Aryne generated under the acidic conditions underwent chemoselective cycloaddition with a furan in the presence of a basic arynophile, namely an amine. Hammett plot analyses revealed that an aryne generation mechanism induced by (±)-CSA is distinct from the mechanism induced by silica gel.
In the present study, four novel ginsenosides fatty acid and aromatic acid derivatives were designed and synthesized, and their cytotoxic effects on human ovarian carcinoma cells (SKOV3) were assessed using the MTT assay. The results demonstrated that all derivatives inhibited SKOV3 cell growth, and Compound 3 showed the most outstanding anti-proliferative effect on SKOV3 cells. The IC50 value of Compound 3 was 33.8 ± 2.21 μM, less than half of that of cis-platinum (70.1 ± 7.64 μM). Subsequent analysis revealed that Compound 3 could promote SKOV3 cell apoptosis, and the percentage of apoptotic cell population increased with increasing Compound 3 concentrations. In addition, the expression ratios of Bax/Bcl-2, cleaved-Caspase-3/Caspase-3 and cleaved-Caspase-9/Caspase-9 were gradually elevated in Compound 3-treated SKOV3 cells compared with control cells. Furthermore, translocation of Bax to mitochondria was associated with the release of Cytochrome C. Molecular docking analysis revealed three hydrogen-bonds existed in Compound 3 with PARP receptor (PDB code: 5DSY), which may be the target of the anti-ovarian cancer effect of Compound 3. Altogether, our study indicates that Compound 3 induces SKOV3 cell apoptosis via ROS-dependent mitochondrial pathway, and can serve as an anti-cancer agent for treating ovarian carcinoma.
Cationic liposomal formulations of the telomeric G-quadruplex stabilizing ligand, 13-(2-naphthylmethoxy)berberine bromide (1), have been developed with the purpose of delivering 1 into the nucleus of cancer cells for potential telomere targeting. Berberine derivative 1 was encapsulated in various cationic lipids 2-4 by the thin film evaporation method; these lipids are cationic after amine protonation. The most appropriate liposomal berberine formulation was that of 1 and the cholesterol derived cationic lipid 4 in a weight ratio of 1:20 with 76.5% encapsulation efficiency of 1. Cellular uptake studies in the HeLa and HT-29 cancer cells line showed that the liposomal berberine derivative uptake in the cells was higher and more stable than for berberine derivative 1 alone while free 1 was completely decomposed in the cells within 60 min exposure to the cells. Anticancer activity of the liposomal berberine derivative 1 based on 4 was greater than that for the free berberine derivative 1 in the MCF-7, HeLa and HT-29 cell line by 2.3-, 4.9- and 5.3-fold, respectively, and also, interestingly, superior to the anticancer drug doxorubicin against the HT29 cancer cell line.
Both iontophoresis (IP) and electroporation (EP) can be utilized to increase the penetration of relatively high molecular pharmaceutical and/or cosmeceutical compounds into the stratum corneum (SC), the uppermost layer of the skin. However, few reports exist on which molecular weights are capable of penetrating the SC, although low molecular compounds of less than 500 Da have been found to readily permeate the skin barrier. In our investigation, we applied fluorescein amine-labeled sodium hyaluronate to porcine aural skin after treatment by IP alone or EP + IP. Each layer of the SC was then tape stripped several times. The stripped SC sheets were observed using a confocal laser scanning microscope to determine the relative amounts of sodium hyaluronate present. The results confirmed that the molecular weight of sodium hyaluronate that penetrated the SC was higher with EP + IP than with IP alone. A high correlation was also established between the quantity of sodium hyaluronate that penetrated and its molecular weight following combined EP + IP treatment.