Structure Diversity and Properties of Some Bola-like Natural Products.

In their shapes, molecules of some bipolar metabolites resemble the so-called bola, a hunting weapon of the South American inhabitants, consisting of two heavy balls connected to each other by a long flexible cord. Herein, we discuss the structures and properties of these natural products (bola-like compounds or bolaamphiphiles), containing two polar terminal fragments and a non-polar chain (or chains) between them, from archaea, bacteria, and marine invertebrates. Additional modifications of core compounds of this class, for example, interchain and intrachain cyclization, hydroxylation, methylation, etc.

In Silico Prediction of Alkaline Phosphatase Interaction with the Natural Inhibitory 5-Azaindoles Guitarrin C and D.

The natural 5-azaindoles, marine sponge guitarrin C and D, were observed to exert inhibitory activity against a highly active alkaline phosphatase (ALP) CmAP of the PhoA family from the marine bacterium , with IC values of 8.5 and 110 µM, respectively. The superimposition of CmAP complexes with -nitrophenyl phosphate (NPP), a commonly used chromogenic aryl substrate for ALP, and the inhibitory guitarrins C, D, and the non-inhibitory guitarrins A, B, and E revealed that the presence of a carboxyl group at C6 together with a hydroxyl group at C8 is a prerequisite for the inhibitory effect of 5-azaindoles on ALP activity.

Stonikacidin A, an Antimicrobial 4-Bromopyrrole Alkaloid Containing L-Idonic Acid Core from the Northwestern Pacific Marine Sponge .

Stonikacidin A (), the first representative of a new class of 4-bromopyrrole alkaloids containing an aldonic acid core, was isolated from the marine sponge . The compound is named in honor of Prof. Valentin A.

Molecular Cloning, Heterologous Expression, Purification, and Evaluation of Protein-Ligand Interactions of CYP51 of Azole-Resistant Fungal Strain.

Due to the increasing prevalence of fungal diseases caused by fungi of the genus and the development of pathogen resistance to available drugs, the need to find new effective antifungal agents has increased. Azole antifungals, which are inhibitors of sterol-14α-demethylase or CYP51, have been widely used in the treatment of fungal infections over the past two decades. Of special interest is the study of CYP51, since this fungus exhibit resistance not only to azoles, but also to other antifungal drugs and there is no available information about the ligand-binding properties of CYP51 of this pathogen.

Rhizochalinin Exhibits Anticancer Activity and Synergizes with EGFR Inhibitors in Glioblastoma In Vitro Models.

Rhizochalinin (Rhiz) is a recently discovered cytotoxic sphingolipid synthesized from the marine natural compound rhizochalin. Previously, Rhiz demonstrated high in vitro and in vivo efficacy in various cancer models. Here, we report Rhiz to be highly active in human glioblastoma cell lines as well as in patient-derived glioma-stem like neurosphere models.

Assimiloside A, a Glycolipid with Immunomodulatory Activity from the Northwestern Pacific Marine Sponge .

Assimiloside A (), an unprecedented marine glycolipid containing a γ-lactone of 4,16,26-trihydroxy C fatty acid as an aglycon and a trisaccharide carbohydrate moiety, was isolated from the marine sponge . Its structure was elucidated by NMR spectroscopy, mass spectrometry, chemical transformations, and ECD spectroscopy combined with time-dependent density functional theory calculations. Assimiloside A at nontoxic concentrations of 0.

Novel GSK-3β Inhibitor Neopetroside A Protects Against Murine Myocardial Ischemia/Reperfusion Injury.

Recent trends suggest novel natural compounds as promising treatments for cardiovascular disease. The authors examined how neopetroside A, a natural pyridine nucleoside containing an α-glycoside bond, regulates mitochondrial metabolism and heart function and investigated its cardioprotective role against ischemia/reperfusion injury. Neopetroside A treatment maintained cardiac hemodynamic status and mitochondrial respiration capacity and significantly prevented cardiac fibrosis in murine models.

New Guanidine Alkaloids Batzelladines O and P from the Marine Sponge Induce Apoptosis and Autophagy in Prostate Cancer Cells.

Two new guanidine alkaloids, batzelladines O () and P (), were isolated from the deep-water marine sponge The structures of these metabolites were determined by NMR spectroscopy, mass spectrometry, and ECD. The isolated compounds exhibited cytotoxic activity in human prostate cancer cells PC3, PC3-DR, and 22Rv1 at low micromolar concentrations and inhibited colony formation and survival of the cancer cells. Batzelladines O () and P () induced apoptosis, which was detected by Western blotting as caspase-3 and PARP cleavage.

Streptocinnamides A and B, Depsipeptides from sp. KMM 9044.

The bacterium sp. KMM 9044 from a sample of marine sediment collected in the northwestern part of the Sea of Japan produces highly chlorinated depsiheptapeptides streptocinnamides A () and B (), representatives of a new structural group of antibiotics. The structures of and were determined using nuclear magnetic resonance and mass spectrometry studies and confirmed by a series of chemical transformations.

Toporosides A and B, Cyclopentenyl-Containing ω-Glycosylated Fatty Acid Amides, and Toporosides C and D from the Northwestern Pacific Marine Sponge .

Toporosides A-D (-), new ω-glycosylated fatty acid amides, were isolated from the sponge . The structures of these compounds, including absolute configurations of stereogenic centers, were established using analysis of 1D and 2D NMR, ECD, and HR mass spectra as well as chemical transformations. Toporosides A () and B () are the first lipids containing a cyclopentenyl α,β-unsaturated carbonyl moiety in the polymethylene chain.

Oceanalin B, a Hybrid α,ω-Bifunctionalized Sphingoid Tetrahydroisoquinoline β-Glycoside from the Marine Sponge sp.

Oceanalin B (), an α,ω-bipolar natural product belonging to a rare family of sphingoid tetrahydoisoquinoline β-glycosides, was isolated from the EtOH extract of the lyophilized marine sponge sp. as the second member of the series after oceanalin A () from the same animal. The compounds are of particular interest due to their biogenetically unexpected structures as well as their biological activities.

Gracilosulfates A-G, Monosulfated Polyoxygenated Steroids from the Marine Sponge .

Seven new polyoxygenated steroids belonging to a new structural group of sponge steroids, gracilosulfates A-G (-), possessing 3--sulfonato, 56 epoxy (or 5(6)-dehydro), and 4,23-dihydroxy substitution patterns as a common structural motif, were isolated from the marine sponge Their structures were determined by NMR and MS methods. The compounds , and inhibited the expression of prostate-specific antigen (PSA) in 22Rv1 tumor cells.

Marine alkaloid monanchoxymycalin C: a new specific activator of JNK1/2 kinase with anticancer properties.

Monanchoxymycalin C (MomC) is a new marine pentacyclic guanidine alkaloid, recently isolated from marine sponge Monanchora pulchra by us. Here, anticancer activity and mechanism of action was investigated for the first time using a human prostate cancer (PCa) model. MomC was active in all PCa cell lines at low micromolar concentrations and induced an unusual caspase-independent, non-apoptotic cell death.

Urupocidin C: a new marine guanidine alkaloid which selectively kills prostate cancer cells via mitochondria targeting.

New bicyclic guanidine alkaloid, urupocidin C (Ur-C) along with the previously known urupocidin A (Ur-A) were isolated from the rare deep-sea marine sponge Monanchora pulchra, harvested in Northwestern Pacific waters. The unique structure of Ur-C was elucidated using 1D and 2D NMR spectroscopy as well as mass spectra. We discovered a promising selectivity of both alkaloids for human prostate cancer (PCa) cells, including highly drug-resistant lines, compared to non-malignant cells.

Leptogorgins A-C, Humulane Sesquiterpenoids from the Vietnamese Gorgonian sp.

Leptogorgins A-C (-), new humulane sesquiterpenoids, and leptogorgoid A (), a new dihydroxyketosteroid, were isolated from the gorgonian sp. collected from the South China Sea. The structures were established using MS and NMR data.

Application of Oxidative and Reductive Transformations in the Structure Determination of Marine Natural Products.

This review highlights the application of oxidative and reductive chemical transformations in the structure determination of complex marine natural products, including their absolute configurations. Workability of the Baeyer-Villiger reaction, ozonolysis, periodate oxidation, hydrogenolysis, and reductive amination, as well as other related chemical transformations, are discussed.

Cyclobutastellettolides A and B, C Norterpenoids from a sp. Marine Sponge.

Two novel C terpenoids (, ) with an unprecedented carbon skeleton () were isolated from a sp. sponge collected from Vietnamese waters. Their structures and absolute configurations were established by extensive NMR, MS, and ECD analyses together with quantum chemical modeling and biogenetic considerations.

New Trisulfated Steroids from the Vietnamese Marine Sponge and Their PSA Expression and Glucose Uptake Inhibitory Activities.

Seven new unusual polysulfated steroids-topsentiasterol sulfate G (), topsentiasterol sulfate I (), topsentiasterol sulfate H (), bromotopsentiasterol sulfate D (), dichlorotopsentiasterol sulfate D (), bromochlorotopsentiasterol sulfate D (), and 4-hydroxyhalistanol sulfate C (), as well as three previously described-topsentiasterol sulfate D (), chlorotopsentiasterol sulfate D () and iodotopsentiasterol sulfate D () have been isolated from the marine sponge . Structures of these compounds were determined by detailed analysis of 1D- and 2D-NMR and HRESIMS data, as well as chemical transformations. The effects of the compounds on human prostate cancer cells PC-3 and 22Rv1 were investigated.

Guitarrins A-E and Aluminumguitarrin A: 5-Azaindoles from the Northwestern Pacific Marine Sponge Guitarra fimbriata.

Guitarrins A-E (1-5), the first natural 5-azaindoles, and aluminumguitarrin A (1a), the first aluminum-containing compound from marine invertebrates, were isolated from the sponge Guitarra fimbriata. The structures of these compounds were established using detailed analysis of 1D and 2D NMR data, mass spectra, and X-ray analysis of 1 and 1a. Compound 3 was proved to be a natural inhibitor of alkaline phosphatase.

Melonoside B and Melonosins A and B, Lipids Containing Multifunctionalized ω-Hydroxy Fatty Acid Amides from the Far Eastern Marine Sponge Melonanchora kobjakovae.

Melonoside B (1) and melonosins B (2) and A (3), new lipids based on polyoxygenated fatty acid amides, and known melonoside A (4) were isolated from two different collections of the marine sponge Melonanchora kobjakovae. The structures of these compounds, including their absolute configurations, were established using detailed analysis of 1D and 2D NMR, ECD, and mass spectra as well as chemical transformations. Melonosins 2 and 3 inhibit AP-1- and NF-kB-dependent transcriptional activities in JB6 Cl41 cells at noncytotoxic concentrations, demonstrating potential cancer preventive activity.

Synthesis and anticancer activity of the derivatives of marine compound rhizochalin in castration resistant prostate cancer.

Development of resistance to standard therapies complicates treatment of advanced prostate cancer. Alternative splicing variants of the androgen receptor (AR), e.g.

Absolute Configuration of the Cytotoxic Marine Alkaloid Monanchocidin A.

The absolute configuration of the cytotoxic guanidine alkaloid monanchocidin A with 11 stereogenic centers from the marine sponge Monanchora pulchra was determined as 5 R, 8 S, 10 S, 13 R, 14 S, 15 R, 19 R, 23 R, 37 S, 42 S, 43 R after extensive reductive degradation and conversion of the resulting alcohols to MTPA derivatives.

Monanchoxymycalin C with anticancer properties, new analogue of crambescidin 800 from the marine sponge .

A new pentacyclic guanidine alkaloid, monanchoxymycalin C () was isolated from a new collection of marine sponge along with the known monanchoxymycalin A (). The structure of was elucidated on the basis of spectroscopic data. Monanchoxymycalin C exhibits cytotoxic activity against human cancer HeLa cells at low micromolar concentrations, induces apoptosis-related death of malignant cells and inhibits cancer cell colony formation.

Lissodendoric Acids A and B, Manzamine-Related Alkaloids from the Far Eastern Sponge Lissodendoryx florida.

The first representatives of a new group of manzamine-related alkaloids with a previously unknown skeletal systems, namely, lissodendoric acids A (1) and B (2), were isolated from the sponge Lissodendoryx florida collected from the Sea of Okhotsk. The structures and absolute configurations have been elucidated by extensive spectroscopic analysis together with chemical transformations and quantum-chemical modeling. The lissodendoric acids show a potent capability to decrease the production of reactive oxygen species in neuroblastoma Neuro 2a and somewhat increase the survival of these cells upon treatment with 6-hydroxydopamine (an in vitro antiparkinson biotest).