Cytotoxic halogenated monoterpenes from <i>Plocamium cartilagineum</i>

<p>As a result of our efforts to identify bioactive agents from marine algae, we have isolated and identified one new halogenated monoterpene <b>1</b> [(-)-(5<i>E</i>,7<i>Z</i>)-348-trichloro-7-dichloromethyl-3-methyl-157-octatriene] in addition to three known compounds (<b>2</b>, <b>3</b> and <b>4</b>) from the red alga <i>Plocamium cartilagineum</i> collected by hand from the eastern coast of South Africa. Compound <b>1</b> was found to be active as a cytotoxic agent in human lung cancer (NCI-H460) and mouse neuro-2a cell lines (IC₅₀ 4 μg/mL). Two of these compounds (<b>3</b> and <b>4</b>) were found to have cytotoxic activity in other cell line assays, especially against human leukaemia and human colon cancers (IC₅₀ 1.3 μg/mL). None of these metabolites were active as sodium channel blockers or activators. All structures were determined by spectroscopic methods (UV, IR, LRMS, HRMS, 1D NMR and 2D NMR). 1D and 2D NOE experiments were carried out on these compounds to confirm the geometry of the double bonds.</p

Investigation of the Physical and Bioactive Properties of Bromo- and Iodo-Containing Sponge-Derived Compounds Possessing an Oxyphenylethanamine Core

This research set out to identify compounds from marine sponges that can act as bacterial virulence blockers. Extracts from a total of 80 sponges collected from throughout Indonesia were screened in a high-throughput NF-κB-based screen that identifies compounds capable of inhibiting the bacterial type III secretion system (T3SS) in <i>Yersinia pseudotuberculosis.</i> An extract that was shown to inhibit T3SS-driven NF-κB expression was obtained from an <i>Iotrochota</i> cf. <i>iota</i> sponge and was the source of seven new bromo- and iodo-containing compounds, all of which contain a 2-(4-oxyphenyl)­ethan-1-amine core. Five were determined to be new compounds and named enisorines A–E (<b>1</b>–<b>5</b>). The remaining two were determined to be new hemibastadinol analogues named (+)-1-<i>O</i>-methylhemibastadinol 2 (<b>6</b>) and (+)-1-<i>O</i>-methylhemibastadinol 4 (<b>7</b>). All seven compounds inhibited T3SS-dependent YopE secretion and did not affect the growth or metabolic activity of <i>Y. pseudotuberculosis</i>. The most potent inhibitors of T3SS activity were enisorine C (<b>3</b>), enisorine E (<b>5</b>), and (+)-1-<i>O</i>-methylhemibastadinol 2 (<b>6</b>), all of which inhibited YopE secretion by >50% at 30 μM

Integrating Molecular Networking and Biological Assays To Target the Isolation of a Cytotoxic Cyclic Octapeptide, Samoamide A, from an American Samoan Marine Cyanobacterium

Integrating LC-MS/MS molecular networking and bioassay-guided fractionation enabled the targeted isolation of a new and bioactive cyclic octapeptide, samoamide A (<b>1</b>), from a sample of cf. <i>Symploca</i> sp. collected in American Samoa. The structure of <b>1</b> was established by detailed 1D and 2D NMR experiments, HRESIMS data, and chemical degradation/chromatographic (e.g., Marfey’s analysis) studies. Pure compound <b>1</b> was shown to have in vitro cytotoxic activity against several human cancer cell lines in both traditional cell culture and zone inhibition bioassays. Although there was no particular selectivity between the cell lines tested for samoamide A, the most potent activity was observed against H460 human non-small-cell lung cancer cells (IC₅₀ = 1.1 μM). Molecular modeling studies suggested that one possible mechanism of action for <b>1</b> is the inhibition of the enzyme dipeptidyl peptidase (CD26, DPP4) at a reported allosteric binding site, which could lead to many downstream pharmacological effects. However, this interaction was moderate when tested in vitro at up to 10 μM and only resulted in about 16% peptidase inhibition. Combining bioassay screening with the cheminformatics strategy of LC-MS/MS molecular networking as a discovery tool expedited the targeted isolation of a natural product possessing both a novel chemical structure and a desired biological activity