Halogenated Indole Alkaloids from Marine Invertebrates

Pauletti, Patrícia Mendonça; Cintra, Lucas Silva; Braguine, Caio Guedes; Filho, Ademar A. Da Silva; Silva, Márcio Luís Andrade e; Cunha, Wilson Roberto; Januário, Ana Helena

doi:10.3390/md8051526

Cited by 89 publications

(57 citation statements)

References 69 publications

(134 reference statements)

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“…Hawksbill turtles, based on their trophic level of eating filterfeeding sponges, were expected to have lower PFOS levels than loggerheads and similar or lower levels than leatherbacks. Although sponges are known to contain unique natural chemicals, many of which are halogenated [16], PFOS and the other PFCs are anthropogenic [1]. One possible explanation for the unexpected species differences may have to do with a different capture location for the hawksbills.…”

Section: Discussionmentioning

confidence: 99%

Perfluoroalkyl contaminants in plasma of five sea turtle species: Comparisons in concentration and potential health risks

Keller

Ngai

McNeill

et al. 2012

Enviro Toxic and Chemistry

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Abstract-The authors compared blood plasma concentrations of 13 perfluoroalkyl contaminants (PFCs) in five sea turtle species with differing trophic levels. Wild sea turtles were blood sampled from the southeastern region of the United States, and plasma was analyzed using liquid chromatography tandem mass spectrometry. Mean concentrations of perfluorooctane sulfonate (PFOS), the predominant PFC, increased with trophic level from herbivorous greens (2.41 ng/g), jellyfish-eating leatherbacks (3.95 ng/g), omnivorous loggerheads (6.47 ng/g), to crab-eating Kemp's ridleys (15.7 ng/g). However, spongivorous hawksbills had surprisingly high concentrations of PFOS (11.9 ng/g) and other PFCs based on their trophic level. These baseline concentrations of biomagnifying PFCs demonstrate interesting species and geographical differences. The measured PFOS concentrations were compared with concentrations known to cause toxic effects in laboratory animals, and estimated margins of safety (EMOS) were calculated. Small EMOS (<100), suggestive of potential risk of adverse health effects, were observed for all five sea turtle species for immunosuppression. Estimated margins of safety less than 100 were also observed for liver, thyroid, and neurobehavorial effects for the more highly exposed species. These baseline concentrations and the preliminary EMOS exercise provide a better understanding of the potential health risks of PFCs for conservation managers to protect these threatened and endangered species.

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Section: Discussionmentioning

confidence: 99%

Perfluoroalkyl contaminants in plasma of five sea turtle species: Comparisons in concentration and potential health risks

Keller

Ngai

McNeill

et al. 2012

Enviro Toxic and Chemistry

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“…Numerous natural drugs (Smit, 2004;Wang et al, 2005;Cabrita et al, 2010) and an increasing number of synthetic drug candidates (Hernandes et al, 2010;Pauletti et al, 2010) are halogenated, comprising approximately 20% of low-mass protein ligands accessible in the Protein Data Bank (PDB), and an even larger number of tested protein kinase inhibitors. The growing number of high-resolution structures of protein kinase-ligand complexes aids in silico development of new inhibitors (Niefind et al, 2009;Ibrahim, 2011;Ibrahim, 2012;Lepsik et al, 2013), many of them halogenated.…”

Section: Introductionmentioning

confidence: 99%

Halogen bonds involved in binding of halogenated ligands by protein kinases.

et al. 2016

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Analysis of 664 known structures of protein kinase complexes with halogenated ligands revealed 424 short contacts between a halogen atom and a potential protein X-bond acceptor, the topology and geometry of which were analyzed according to the type of a halogen atom (X = Cl, Br, I) and a putative protein X-bond acceptor. Among 236 identified halogen bonds, the most represented ones are directed to backbone carbonyls of the hinge region and may replace the pattern of ATP-like hydrogen bonds. Some halogen-π interactions with either aromatic residues or peptide bonds, that accompany the interaction with the hinge region, may possibly enhance ligand selectivity. Interestingly, many of these halogen-π interactions are bifurcated. Geometrical preferences identify iodine as the strongest X-bond donor, less so bromine, while virtually no such preferences were observed for chlorine; and a backbone carbonyl as the strongest X-bond acceptor. The presence of a halogen atom in a ligand additionally affects the properties of proximal hydrogen bonds, which according to geometrical parameters get strengthened, when a nitrogen of a halogenated ligand acts as the hydrogen bond donor.

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“…[27] Cleavage of the C2ÀC7 bond [34] of A generates the nine-membered ring framework B,w hich is characteristic of the leuconolam-type natural products 10-12 (Scheme2). Transannular cyclization with bond formation between N1 and C21 produces skeleton C,w hich is the diazafenestrane core structure of leuconoxines 1-8.R ing contraction/enlargement from C21t oC 7b yt he nitrogen atom affords compound D, which delivers the carbon skeleton of mersicarpine E after fragmentation of the four-membered ring of D. [35] Alternatively, C7-C16 connection in structure B leads to meloscine scaffold F,w hich is also accessible via architecture A (ring enlargement of the indole ring).…”

Section: Biosynthesismentioning

confidence: 99%