Design, synthesis, and biological evaluation of novel 3-(thiophen-2-ylthio)pyridine derivatives as potential multitarget anticancer agents.

A series of novel 3-(thiophen-2-ylthio)pyridine derivatives as insulin-like growth factor 1 receptor (IGF-1R) inhibitors was designed and synthesized. IGF-1R kinase inhibitory activities and cytotoxicities against HepG2 and WSU-DLCL2 cell lines were tested. For all of these compounds, potent cancer cell proliferation inhibitory activities were observed, but not through the inhibition of IGR-1R. Selected compounds were further screened against various kinases. Typical compound 22 (50% inhibitory concentration [IC50 ] values, HepG2: 2.98 ± 1.11 µM and WSU-DLCL2: 4.34 ± 0.84 µM) exhibited good inhibitory activities against fibroblast growth factor receptor-2 (FGFR2), FGFR3, epidermal growth factor receptor, Janus kinase, and RON (receptor originated from Nantes), with IC50 values ranging from 2.14 to 12.20 µM. Additionally, the cell-cycle analysis showed that compound 22 could arrest HepG2 cells in the G1/G0 phase. Taken together, all the experiments confirmed that the compounds in this series were multitarget anticancer agents worth further optimizing.

Antioxidant and antimicrobial evaluation of carboxymethylated and hydroxamated degraded polysaccharides from Sargassum fusiforme.

In order to improve the bioactivity of the polysaccharide from Sargassum fusiforme (PSF), the degraded polysaccharide (DPSF) was modified by carboxymethylation, yielding carboxymethylated degraded polysaccharides (CDPSF), which were further modified to generate hydroxamated derivatives (HCDPSF). Both CDPSF and HCDPSF were characterized by Fourier transform infrared spectroscopy. The molecular weight of CDPSF and HCDPSF was found to be 354 kDa and 375 kDa, respectively. The in vitro antioxidant activity of CDPSF and HCDPSF was evaluated by determining the radical scavenging ability and total antioxidant activity. The results indicated that the antioxidant activity of CDPSF and HCDPSF was significantly improved when compared to those of DPSF. Antimicrobial assays indicated that both CDPSF and HCDPSF possessed a marked antimicrobial ability, while DPSF did not exhibit such effects under the same conditions. Such polysaccharide derivatives have potentials in the pharmaceutical and food industries.

Synthesis, iron binding and antimicrobial properties of hexadentate 3-hydroxypyridinones-terminated dendrimers.

Macromolecular chelators have potential applications in the medical area, for instance, in treatment of iron overload-related disorders and in the treatment of external infections. In this investigation, several novel iron(III)-selective hydroxypyridinone hexadentate-terminated first and second generation dendrimeric chelators were synthesized using a convergent strategy. Their iron chelating ability was demonstrated by UV/Visible spectrometry and high resolution mass spectrometry (HRMS). The iron binding affinities were also investigated by the competition with a fluorescent iron chelator CP691. The result indicated that these dendrimers possesses a high affinity for iron with a very high pFe3+ value, which is close to that of an isolated hexadentate unit. These dendrimeric chelators were found to exhibit inhibitory effect on the growth of both Gram-positive and Gram-negative bacteria.

Novel hydroxypyridinone derivatives containing an oxime ether moiety: Synthesis, inhibition on mushroom tyrosinase and application in anti-browning of fresh-cut apples.

A range of hydroxypyridinone derivatives were synthesized starting from kojic acid. Among them, 10 and 11 were found to possess the strongest inhibitory effect on monophenolase activity of mushroom tyrosinase, having IC50 values of 2.04 and 1.60µM, respectively. The IC50 values of 10 and 11 for the inhibition of diphenolase activity of mushroom tyrosinase were determined as 13.89 and 7.99µM, respectively. Investigation of the inhibitory mechanism of these two compounds indicated that the inhibition was reversible and of a competitive-uncompetitive mixed type. The KI and KIS values of 10 were determined to be 24.84 and 32.54µM, respectively, and the corresponding values for 11 being 18.07 and 21.34µM, respectively. The effect of 11 on the browning process of fresh-cut apples was evaluated by measuring the color change and browning index. The results indicated that 11 had a significant effect on controlling the browning of fresh-cut apple slices.

Preparation, antioxidant and antimicrobial evaluation of hydroxamated degraded polysaccharides from Enteromorpha prolifera.

In order to improve the antioxidant and antimicrobial abilities, hydroxamated degraded polysaccharides from Enteromorpha prolifera (HCDPE) were prepared from the corresponding carboxymethylated degraded polysaccharides (CDPE). HCDPE was characterized by FT-IR. The weight-average molecular weight of HCDPE was determined as 55.4kDa. The in vitro antioxidant activity of HCDPE was evaluated by determining the radical (1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl and superoxide anion radicals) scavenging abilities and total antioxidant activity. It was found that DPPH radical scavenging ability and total antioxidant activity of HCDPE were significantly improved compared to those of CDPE. The inhibitory effects of polysaccharides against the five bacterial strains (Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella spp.) were also evaluated by bacterial inhibition zone and minimum inhibitory concentration (MIC) assays. The results indicated that CDPE and HCDPE possess marked antimicrobial ability, while such an effect was not observed for the crude polysaccharides (PE) and the degraded polysaccharides (DPE).