Discovery of pyrazole-carbohydrazide with indole moiety as tubulin polymerization inhibitors and anti-tumor candidates.

In this work, a series of indole-containing pyrazole-carbohydrazide derivatives A1-A25 were synthesized, and their biological activity on tubulin polymerization inhibition and mitotic catastrophe was evaluated. For introducing indole group to CA-4 pattern, the carbohydrazide linker was used for the first time. As the top hit, A18 suggested notable antiproliferation efficacy and tubulin polymerization inhibitory activity. Inferring comparable antitubulin effect with the positive control Colchicine, A18 indicated obviously lower cyto-toxicity. The cell scratch test showed that A18 could block the cell migration, while the confocal imaging depicted that A18 could induce the mitotic catastrophe via a Colchicine-like approach. The docking simulation visualized the probable binding pattern of A18. With the information in this work, some new hints on modification might be involved in further tubulin-related investigations.

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.

Molecular simulations required to target novel and potent inhibitors of cancer invasion.

INTRODUCTION: Computer-aided drug design (CADD) is a computational approach used to discover, develop, and analyze drugs and active molecules with similar biochemical properties. Molecular simulation technology has significantly accelerated drug research and reduced manufacturing costs. It is an optimized drug discovery method that greatly improves the efficiency of novel drug development processes. AREASCOVERED: This review discusses the development of molecular simulations of effective cancer inhibitors and traces the main outcomes of in silico studies by introducing representative categories of six important anticancer targets. The authors provide views on this topic from the perspective of both medicinal chemistry and artificial intelligence, indicating the major challenges and predicting trends. EXPERT OPINION: The goal of introducing CADD into cancer treatment is to realize a highly efficient, accurate, and desired approach with a high success rate for identifying potent drug candidates. However, the major challenge is the lack of a sophisticated data-filtering mechanism to verify bottom data from mixed-quality references. Consequently, despite the continuous development of algorithms, computer power, and interface optimization, specific data filtering mechanisms will become an urgent and crucial issue in the future.