Novel substituted aminoalkylguanidines as potential antihyperglycemic and food intake-reducing agents.

We report the synthesis and evaluation of aminoalkylguanidine analogues and derivatives in C57BL/KsJ db/db diabetic mice, following identification by random screening of 1a and 1b as potential antihyperglycemics and/or modulators of food intake. These compounds are related to galegine, a gamma,gamma-dimethylallylguanidine. Between the newly identified compounds, 1h N-(cyclopropylmethyl)- N'-(4-(aminomethyl)cyclohexylmethyl)guanidine showed the most balanced activity as antihyperglycemic and food intake-reducing agent.

Paclitaxel and docetaxel resistance: molecular mechanisms and development of new generation taxanes.

Taxanes represent one of the most promising classes of anticancer agents. Unfortunately, their clinical success has been limited by the insurgence of cellular resistance, mainly mediated by the expression of the MDR phenotype or by microtubule alterations. However, the remarkable relevance of paclitaxel and docetaxel in clinical oncology stimulated intensive efforts in the last decade to identify new derivatives endowed with improved activities towards resistant tumor cells, resulting in a huge number of novel natural and synthetic taxanes.

Research on L-nucleosides. Synthesis and biological evaluation of a series of L- and D-2',3'-dideoxy-3'-[tris(methylthio)methyl]-beta-pentofuranosyl nucleosides.

Novel nucleoside analogues of both D and L enantiomeric series were prepared by coupling reaction between a 2',3'-dideoxy-3'-modified furanose moiety and four different nucleobases. Though in all cases anomeric mixtures of nucleosides were obtained, the presence of the sterically bulky 3'-tris(methylthio)methyl group allowed a good stereoselectivity level. All the compounds of both enantiomeric series showed high IC(50) values as HSV-1 TK inhibitors and scarce ability to be phosphorylated by HSV-1 TK.