A review, with 386 refs., on polyoxygenated steroids of marine origin, e.g. marine algae, Porifera, Coelenterata, Bryozoa, Mollusca, Echinodermata, Arthropoda, tunicates, and vertebrates (fish)
Callipeltin A (1) is a cyclic depsidecapeptide from a
shallow water sponge of the genus Callipelta
(order
Lithistida), collected in the waters off New Caledonia. The
structure of callipeltin A (1), which possesses
the
N-terminus blocked with a β-hydroxy acid, and the C-terminus
lactonized with a threonine residue, was determined
by interpretation of spectral data, chemical degradation, and
evaluation of the amino acids obtained by acid hydrolysis.
Along with four common l-, one d-, and two
N-methyl amino acids, it contains three new amino acid
residues:
β-methoxytyrosine (βOMeTyr),
(2R,3R,4S)-4-amino-7-guanidino-2,3-dihydroxyheptanoic
acid (AGDHE), and (3S,4R)-3,4-dimethyl-l-glutamine. Callipeltin A (1)
has been found to protect cells infected by human
immunodeficiency
(HIV) virus.
Biodiversity in the seas is only partly explored, although marine organisms are excellent sources for many industrial products. Through close co-operation between industrial and academic partners, it is possible to successfully collect, isolate and classify marine organisms, such as bacteria, fungi, micro- and macroalgae, cyanobacteria, and marine invertebrates from the oceans and seas globally. Extracts and purified compounds of these organisms can be studied for several therapeutically and industrially significant biological activities, including anticancer, anti-inflammatory, antiviral, antibacterial, and anticoagulant activities by applying a wide variety of screening tools, as well as for ion channel/receptor modulation and plant growth regulation. Chromatographic isolation of bioactive compounds will be followed by structural determination. Sustainable cultivation methods for promising organisms and biotechnological processes for selected compounds can be developed, as well as biosensors for monitoring the target compounds. The (semi)synthetic modification of marine-based bioactive compounds produces their new derivatives, structural analogs and mimetics that could serve as hit or lead compounds and be used to expand compound libraries based on marine natural products. The research innovations can be targeted for industrial product development in order to improve the growth and productivity of marine biotechnology. Marine research aims at a better understanding of environmentally conscious sourcing of marine biotechnology products and increased public awareness of marine biodiversity. Marine research is expected to offer novel marine-based lead compounds for industries and strengthen their product portfolios related to pharmaceutical, nutraceutical, cosmetic, agrochemical, food processing, material and biosensor applications.
Bile acids exert genomic and nongenomic effects by interacting with membrane G-protein-coupled receptors, including the bile acid receptor GP-BAR1, and nuclear receptors, such as the farnesoid X receptor (FXR). These receptors regulate overlapping metabolic functions; thus, GP-BAR1/FXR dual agonists, by enhancing the biological response, represent an innovative strategy for the treatment of enteroendocrine disorders. Here, we report the design, total synthesis, and in vitro/in vivo pharmacological evaluation of a new generation of dual bile acid receptor agonists, with the most potent compound, 19, showing promising pharmacological profiles. We show that compound 19 activates GP-BAR1, FXR, and FXR regulated genes in the liver, increases the intracellular concentration of cAMP, and stimulates the release of the potent insulinotropic hormone GLP-1, resulting in a promising drug candidate for the treatment of metabolic disorders. We also elucidate the binding mode of the most potent dual agonists in the two receptors through a series of computations providing the molecular basis for dual GP-BAR1/FXR agonism.
A cytotoxic glycoside macrolide, callipeltoside A, has been
isolated from the marine lithistid sponge
Callipelta sp., collected off New Caledonia. Structural
assigment was accomplished through extensive 2D NMR
spectroscopy. The complete relative stereochemistry is proposed
from the analysis of ROESY and NOE difference
experiments. Callipeltoside A (1) represents the first
member of a new class of marine-derived macrolides,
containing
unusual structural features including a
4-amino-4,6-dideoxy-2-O,3-C-dimethyl-α-talopyranosyl-3,4-urethane
unit.
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