Discovery of novel indole-1,2,4-triazole derivatives as tubulin polymerization inhibitors.

A series of novel indole-1,2,4-triazole derivatives have been designed, synthesized, and evaluated as potential tubulin polymerization inhibitors. The top hit 12, bearing the 3,4,5-trimethoxyphenyl moiety, exhibited substantial anti-proliferative activity against HepG2, HeLa, MCF-7, and A549 cells in vitro with IC50 values of 0.23 ± 0.08 µM, 0.15 ± 0.18 µM, 0.38 ± 0.12 µM, and 0.30 ± 0.13 µM, respectively. It also inhibited tubulin polymerization with the IC50 value of 2.1 ± 0.12 µM, which was comparable with that of the positive controls. Furthermore, compound 12 regulated the expression of cell cycle-related proteins (Cyclin B1, Cdc25c, and Cdc2) and apoptosis-related proteins (Bcl-2, Bcl-x, and Mcl-1). Mechanistically, compound 12 could arrest cell cycle at the G2/M phase, thus induce an increase of apoptotic cell death. In addition, molecular docking hinted the possible interaction mode of compound 12 into the colchicine binding site of tubulin heterodimers. According to the applications of microtubule-targeting agents in both direct and synergistic cancer therapies, we hope this work might be of significance for future researches.

Structural and functional investigation on stem and peel polysaccharides from different varieties of pitaya.

Varieties of plant species may affect the composition and structures of the polysaccharides, thus have an impact on their chemical properties and biological activities. Herein, the present study comparatively evaluated the differences in the chemical composition, morphological structures, antioxidant activity, and anti-inflammatory activity of the stem and peel polysaccharides from different varieties of pitaya. The FT-IR and NMR spectra indicated that the six polysaccharides had similar structural features, whereas the physicochemical characterization showed that they differed significantly in terms of the monosaccharide composition, molecular weight, and surface morphology. In addition, different varieties of pitaya polysaccharides exhibited different antioxidant activities and similar anti-inflammatory activities. These data suggested that varietal differences resulted in pitaya stem and peel polysaccharides with different monosaccharide compositions and molecular weights, thus led to different antioxidant activities and protection against oxidative damage, while similar structural features were closely related to their similar anti-inflammatory activities. Therefore, the study of the stem and peel polysaccharides from different varieties of pitaya can help us to better understand the relationship between their composition and structure and their biological activities. In addition, pitaya stem and peel polysaccharides have the potential to act as antioxidants or to treat inflammatory damage.

Discussion on the Structural Modification and Anti-tumor Activity of Flavonoids.

Flavonoids are secondary metabolites of plants. In general，most flavonoids are combined with glucosides and have extremely complex molecular structures. In nature, these flavonoids have a variety of biological activities, such as anti-oxidation，anti-virus, anti-tumor, scavenging free radicals, etc.; however，due to poor solubility and stability of flavonoids，their bioavailability is limited. The drug design method is used to modify the structure of flavonoids to give them special properties. At present, flavonoids have shown broad application prospects in treating tumors, inhibiting proliferation, migration, invasion, angiogenesis, and multi-drug resistance of tumors and have become a research hotspot.