Microtubules continue to be one of the most successful anticancer drug targets and a favorite hit for many naturally occurring molecules. While two representative agents in clinical use, taxanes vinca alkaloids, come from terrestrial sources, sea has also proven rich source new tubulin-binding We describe herein first isolation, structural elucidation total synthesis totally polyketides isolated Madagascan sponge Lithoplocamia lithistoides . Both PM050489 PM060184 show antimitotic properties...

Three unusual new steroid thioesters, parathiosteroids A−C (1a−3a), were isolated from the 2-propanol extract of soft coral Paragorgia sp. collected in Madagascar. Their structures, determined by detailed spectroscopic analysis, confirmed synthesis and represent first isolation natural steroids bearing a C22 thioester their side chain. These compounds displayed cytotoxicity against panel three human tumor cell lines at micromolar level. The preparation several analogues revealed...

The marine environment is a rich source of metabolites with potential therapeutic properties and applications for humans. Here we describe the first isolation, solid-phase total synthesis, full structural assignment new class cyclodepsipeptides from Madagascan sponge Ecionemia acervus that shows in vitro cytotoxic activities at submicromolar concentrations. Seven structures belonging to family compounds, given general name stellatolides, were characterized. sequence stereochemistry all amino...

Two new cyclic depsipeptides, pipecolidepsins A and B (1 2), have been isolated from the sponge Homophymia lamellosa collected off coast of Madagascar. Their structures were determined by a combination NMR experiments LC-MS analysis amino acid fragments obtained hydrolysis derivatization using Marfey's reagent. In addition to several common acids, these peptides contain unusual residues, including 2-amino-3-hydroxy-4,5-dimethylhexanoic acid, 3-ethoxyasparagine, 3,4-dimethylglutamine,...

A novel compound, named plumisclerin (1), was isolated from samples of the soft coral Plumigorgia terminosclera collected at Mayotte Island. The compound possesses plumisclerane carbon skeleton, including a tricyclo[4,3,1,0(1,5)]decane ring. Its structure and relative stereochemistry were elucidated by extensive spectroscopic analysis, HREIMS, COSY, HSQC, HMBC, TOCSY, NOESY experiments. In addition, displayed in vitro cytotoxicity against selected cancer cell lines.

This paper reports the studies of components an undescribed sponge in genus Pachastrissa sp., collected along Djibouti coast. The extract showed activity against Candida albicans. Six new bengazoles (1−6) and a bengamide, named bengamide L (16), addition to known (7−11), bengamides A (12), B (13), E (14), F (15), lactone (17) are described this paper. All structures were determined on basis spectroscopic studies.

Two cytotoxic alkaloids, discorhabdins L (1) and I (2), were isolated from Latrunculia brevis their structures assigned on the basis of detailed spectroscopic analysis comparison with known metabolites R (5), D (6), B (4). Compounds 1 2 showed strong in vitro cytotoxicity against a panel 14 tumor cell lines.

Onchidin B (4) is a cyclic depsipeptide isolated from the pulmonate mollusc Onchidium sp. Its structure was determined by extensive 2D-NMR, FABMS, tandem FAB MS/MS, selective hydrolysis, and synthesis. It contains four α-amino acids [two units of N-methyl valine (MeVal), two proline (Pro)], α-hydroxy 2-hydroxyisovaleric (Hiv), 2-hydroxy-3-methylpentanoic acid moieties (Hmp)] new β-hydroxy acid: 3-hydroxy-2-methyloct-7-ynoic (Hymo)]. Selective hydrolysis direct comparison chiral GC-MS with...

Four new antitumor pyranones, PM050511 (1), PM050463 (2), PM060054 (3), and PM060431 (4), were isolated from the cell extract of marine-derived Streptomyces albus POR-04-15-053. Their structures elucidated by a combination spectroscopic methods, mainly 1D 2D NMR HRESIMS. They consist an α-methoxy-γ-pyrone ring containing highly substituted tetraene side chain glycosylated at C-10 in case 1 4. Compounds 4 displayed strong cytotoxicity against three human tumor lines with GI50 values...

Abstract New cytotoxic polyketide macrolides named phormidolides B and C were isolated from a marine sponge of the Petrosiidae family collected off coast Pemba (Tanzania). The isolation, structure elucidation, enantioselective synthesis three diastereomers macrocyclic core is described herein. synthetic methodology started 2‐deoxy‐ D ‐ribose or L afforded desired macrocycles with high enantiomeric purity. key step formation Z ‐trisubstituted double bond using Julia–Kocienski olefination....

QM/NMR-DFT (quantum mechanics combined with nuclear magnetic resonance parameters calculated by density functional theory approximations) studies allowed us to link two stereoclusters separated methylene groups present in the new meroditerpenes halioxepine B (2) and C (3) known (1), isolated from Indonesian sponges of genus Haliclona (Reniera). DP4 DP4+ probabilities were used discriminate diastereotopic arrangements stereoclusters, whose unconnected relative configurations determined ROESY...

PM100117 and PM100118 are glycosylated polyketides with remarkable antitumor activity, which derive from the marine symbiotic actinobacteria Streptomyces caniferus GUA-06-05-006A. Structurally, composed of a macrocyclic lactone, three deoxysugar units naphthoquinone (NQ) chromophore that shows clear structural similarity to menaquinone. Whole-genome sequencing S. GUA-06-05-006A has enabled identification biosynthesis gene cluster, been characterized on basis bioinformatics genetic...

Two new bromotyrosine derivatives, anomoian B (1) and aplyzanzine (2), were isolated, respectively, from the organic extracts of a Verongida sponge belonging to Hexadella genus two-sponge association (Jaspis sp. Bubaris sp.), both collected off coast Indonesia. The planar structure 1 2 was determined by 1D 2D NMR experiments high-resolution mass spectrometry, while their absolute stereochemistry assigned comparison with optical rotation values known bromotyrosines chemical degradation. Both...

Two new indolocarbazole alkaloids, 7-oxo-3,8,9-trihydroxystaurosporine (1) and 7-oxo-8,9-dihydroxy-4'-N-demethylstaurosporine (2), were isolated from samples of the marine ascidian Cystodytes solitus. Their structures determined by a combination spectroscopic techniques, including (+)-HRMALDITOFMS 1D 2D NMR spectroscopy, comparison with published data for related structures. Both compounds displayed strong cytotoxicity against three human tumor cell lines.

Lanesoic acid (1) was isolated and characterized from Theonella sp. during PharmaMar's ongoing program to study cytotoxic substances marine sources. Its planar structure, elucidated by spectral analysis (NMR, IR, UV, MS), possesses an unusual skeleton containing a tetrahydropyrimidine cation that is stabilized as zwitterion internal carboxylate counterion. The stereostructure of 1 deduced ROESY-NOESY, J-based configurational (JBCA), density functional theory (DFT) computational calculations...

Two new tryptamine derivatives, granulatamides A (1) and B (2), were isolated from the 2-propanol extract of soft coral Eunicella granulata. Their structures determined on basis detailed spectroscopic analysis comparison with previously published data for similar compounds. Both compounds showed moderate in vitro cytotoxicity against a panel 16 human tumor cell lines.

Two novel oxazole-thiazole containing cyclic hexapeptides, bistratamides M (1) and N (2) have been isolated from the marine ascidian Lissoclinum bistratum (L. bistratum) collected in Raja Ampat (Papua Bar, Indonesia). The planar structure of 1 2 was assigned on basis extensive 1D 2D NMR spectroscopy mass spectrometry. absolute configuration amino acid residues determined by application Marfey's advanced methods after ozonolysis followed acid-catalyzed hydrolysis. interaction between zinc...

Plasma membrane integrity is essential for cell life. Any major break on it immediately induces the death of affected cell. Different molecules were described as disrupting this structure and thus showing antitumor activity. We have previously defined that elisidepsin (Irvalec®, PM02734) inserts self-organizes in plasma tumor cells, inducing a rapid loss integrity, permeabilization necrotic death. Here we show that, sensitive HCT-116 colorectal all these effects are consequence interaction...

Antitumor compounds PM100117 and PM100118 are glycosylated polyketides derived from the marine actinobacteria Streptomyces caniferus GUA-06-05-006A. The organization characterization of PM100117/18 biosynthesis gene cluster has been recently reported.Based on preceding information new genetic engineering data, we have outlined pathway by which glycosylated. Furthermore, these experiments allowed generation novel analogues. Deletion putative glycosyltranferase genes additional presumably...