The interest in 3,4-dihydropyrimidine-2(1)-(thio)ones is increasing every day, mainly due to their paramount biological relevance. The Biginelli reaction is the classical approach to reaching these scaffolds, although the product diversity suffers from some limitations. In order to overcome these restrictions, two main approaches have been devised.
View Article and Find Full Text PDFPhenotypic drug discovery must take advantage of the large amount of clinical data currently available. In this sense, the impact of microRNAs (miRs) on human disease and clinical therapeutic responses is becoming increasingly well documented. Accordingly, it might be possible to use miR-based signatures as phenotypic read-outs of pathological status, for example in cancer.
View Article and Find Full Text PDFMicrotubules continue to be one of the most successful anticancer drug targets and a favorite hit for many naturally occurring molecules. While two of the most successful representative agents in clinical use, the taxanes and the vinca alkaloids, come from terrestrial sources, the sea has also proven to be a rich source of new tubulin-binding molecules. We describe herein the first isolation, structural elucidation and total synthesis of two totally new polyketides isolated from the Madagascan sponge Lithoplocamia lithistoides .
View Article and Find Full Text PDFLack of knowledge of the exact chemical structure of cephalosporin antigenic determinants has hindered clinical interpretation of adverse reactions to these drugs and delayed understanding of the mechanisms involved in the specific recognition and binding of IgE molecules to these antigenic determinants. We further resolve the relationship between structure and activity of proposed antigenic chemicals, including the rational design and synthesis of these haptenic structures. Comparative RAST inhibition studies of the synthesized molecules revealed that they were recognized by IgE antibodies induced by cephalosporin antibiotics.
View Article and Find Full Text PDFThe synthesis of benzylpenicilloyl-containing dendrimers has been achieved by a convenient procedure involving quantitative functionalization of the terminal amino groups of the three Starbust PAMAM generations used (G(n); n = 0, 1, 2). All these densely penicilloylated dendrimers (G(n)P) exhibit similar, simple NMR spectroscopic data suggesting highly symmetric structures and a monodisperse nature, and the results obtained from MALDI-TOF-MS demonstrate their exact chemical composition. The use of PAMAM dendrimers has allowed us to synthesize, for the first time, carrier benzylpenicilloyl conjugates (G(n)P) of precisely defined chemical structure.
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