Thrombin Inhibitors from the Freshwater Cyanobacterium <i>Anabaena compacta</i>

Bioassay-guided investigation of the cyanobacterium <i>Anabaena compacta</i> extracts afforded spumigin J (<b>1</b>) and the known thrombin inhibitor spumigin A (<b>2</b>). The absolute configuration of <b>1</b> was analyzed by advanced Marfey’s methodology. Compounds <b>1</b> and <b>2</b> inhibited thrombin with EC₅₀ values of 4.9 and 2.1 μM, and 0.7 and 0.2 μM in the cathepsin B inhibitory assay, respectively. The MM-GBSA methodology predicted spumigin A with 2<i>S</i>-4-methylproline as the better thrombin inhibitor

Trikentramides A–D, Indole Alkaloids from the Australian Sponge <i>Trikentrion flabelliforme</i>

Chemical investigations of two specimens of <i>Trikentrion flabelliforme</i> collected from Australian waters have resulted in the identification of four new indole alkaloids, trikentramides A–D (<b>9</b>–<b>12</b>). The planar chemical structures for <b>9</b>–<b>12</b> were established following analysis of 1D/2D NMR and MS data. The relative configurations for <b>9</b>–<b>12</b> were determined following the comparison of ¹H NMR data with data previously reported for related natural products. The application of a quantum mechanical modeling method, density functional theory, confirmed the relative configurations and also validated the downfield carbon chemical shift observed for one of the quaternary carbons (C-5a) in the cyclopenta­[<i>g</i>]­indole series. The indole-2,3-dione motif present in trikentramides A–C is rare in nature, and this is the first report of these oxidized indole derivatives from a marine sponge

Will Robots Take Your Job?

A chemoinformatic method was developed to extract nonflat scaffolds embedded in natural products within the Dictionary of Natural Products (DNP). The cedrane scaffold was then chosen as an example of a nonflat scaffold that directs substituents in three-dimensional (3D) space. A cedrane scaffold that has three orthogonal handles to allow generation of 1D, 2D, and 3D libraries was synthesized on a large scale. These libraries would cover more than 50% of the natural diversity of natural products with an embedded cedrane scaffold. Synthesis of three focused natural product-like libraries based on the 3D cedrane scaffold was achieved. A phenotypic assay was used to test the biological profile of synthesized compounds against normal and Parkinson’s patient-derived cells. The cytological profiles of the synthesized analogues based on the cedrane scaffold revealed that this 3D scaffold, prevalidated by nature, can interact with biological systems as it displayed various effects against normal and Parkinson’s patient-derived cell lines