3 research outputs found
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 EC<sub>50</sub> 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 <sup>1</sup>H 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 cyclopentaÂ[<i>g</i>]Âindole 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