Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization.

Based on an (aminoaryl)benzothiazole quinazoline hit structure for kinase inhibition, a systematic optimization program resulted in a lead structure allowing for inhibitory activities in cellular phosphorylation assays in the low nanomolar range.

Computer-aided design of agents that inhibit the cep quorum-sensing system of Burkholderia cenocepacia.

Recent research has provided evidence that interference with bacterial cell-to-cell signaling is a promising strategy for the development of novel antimicrobial agents. Here we report on the computer-aided design of novel compounds that specifically inhibit an N-acyl-homoserine lactone-dependent communication system that is widespread among members of the genus Burkholderia. This genus comprises more than 30 species, many of which are important pathogens of animals and humans.

Discovery of a novel series of DHODH inhibitors by a docking procedure and QSAR refinement.

A novel series of DHODH inhibitors was developed based on a lead which was obtained by a docking procedure and a medicinal chemistry exploration. The activity of the initial lead was improved by a QSAR method to yield low nanomolar inhibitors.

Ancistrolikokine D, a 5,8'-coupled naphthylisoquinoline alkaloid, and related natural products from Ancistrocladus likoko.

A new naphthylisoquinoline alkaloid, ancistrolikokine D, and the likewise 5,8'-coupled alkaloid ancistroealaine A, as well as two further, biosynthetically related, but nitrogen-free natural products, ancistronaphthoic acid B and cis-isoshinanolone, have been isolated from Ancistrocladus likoko J. LEACUTE;ONARD (Ancistrocladaceae). The 5,8'-coupling of the new alkaloids and of the alkaloids isolated earlier hints at a close phylogenetic relationship of A.

5'-O-demethyldioncophylline A, a new antimalarial alkaloid from triphyophyllum peltatum.

From the root bark of Triphyophyllum peltatum, the new naphthylisoquinoline alkaloid 5'-O-demethyldioncophylline A has been isolated. Its otherwise difficult separation from the largely dominating main alkaloid, dioncophylline A, was greatly facilitated by a bromination-benzylation procedure. From the resulting derivative, a crystal structure analysis with an anomalous X-ray diffraction was achieved, allowing confirmation of the full absolute stereostructure of the new alkaloid.