FTIR spectroscopy: a new valuable tool to classify the effects of polyphenolic compounds on cancer cells.

Polyphenolic compounds are an important part of human diet and regular consumption of fruits, vegetables and tea is associated with reduced risk of cancer. Dietary polyphenols display a vast array of cellular effects but the large number of data published in the literature makes it difficult to determine the main mechanisms of action associated and to identify molecules with original mechanisms. Therefore, there is an increasing demand for more systemic approaches in order to obtain a global insight of the biochemical processes mediated by polyphenols.

DYRK1A kinase inhibitors with emphasis on cancer.

Various types of cancers (including gliomas, melanomas, and esophageal, pancreas and non-small-cell lung cancers) display intrinsic resistance to pro-apoptotic stimuli, such as conventional chemotherapy and radiotherapy, and/or the activation of a multidrug resistance phenotype, which are major barriers to effective treatment and lead to poor patient prognosis. The DYRK1A kinase is directly implicated in the resistance of cancer cells to pro-apoptotic stimuli and drives several pathways that enhance proliferation, migration, and the reduction of cell death, leading to very aggressive biological behavior in cancer cell populations. The DYRK1A kinase is also implicated in neurological diseases and in neoangiogenic processes.

N-Aryl-N'-(chroman-4-yl)ureas and thioureas display in vitro anticancer activity and selectivity on apoptosis-resistant glioblastoma cells: screening, synthesis of simplified derivatives, and structure-activity relationship analysis.

A series of chroman derivatives previously reported as potassium channel openers, as well as some newly synthesized simplified structures, were examined for their in vitro effects on the growth of three human high-grade glioma cell lines: U373, T98G, and Hs683. Significant in vitro growth inhibitory activity was observed with 2,2-dimethylchroman-type nitro-substituted phenylthioureas, such as compounds 4o and 4p. Interestingly, most tested phenylureas were found to be slightly less active, but more cell selective (normal versus tumor glial cells, such as 3d, 3e, and 3g), thus less toxic, than the corresponding phenylthioureas.

Synthesis and biological evaluation of analogs of the marine alkaloids granulatimide and isogranulatimide.

A series of pyrrolic analogs and two series of regioisomeric pyrazolic analogs of the marine alkaloids granulatimide and isogranulatimide were prepared. The synthesis of the two first ones was based on the condensation reaction of diversely 5-substituted 3-bromoindoles with pyrrole or pyrazole followed by addition of the intermediates on maleimide or dibromomaleimide, respectively, the so-obtained acyclic adducts being finally photocyclized to the desired analogs. Compounds of the last series were obtained by reacting different 5-substituted-indole-3-glyoxylates with N-Boc-pyrazole-3-acetamide and subsequent photochemical cyclization of the adducts.

Bulbispermine: a crinine-type Amaryllidaceae alkaloid exhibiting cytostatic activity toward apoptosis-resistant glioma cells.

The Amaryllidaceae alkaloid bulbispermine was derivatized to produce a small group of synthetic analogues. These, together with bulbispermine's natural crinine-type congeners, were evaluated in vitro against a panel of cancer cell lines with various levels of resistance to pro-apoptotic stimuli. Bulbispermine, haemanthamine, and haemanthidine showed the most potent antiproliferative activities as determined by the MTT colorimetric assay.