Isolation and Characterization of Anti-Mycobacterial Natural Products from a Petrosia sp. Marine Sponge.

Tuberculosis (TB) is a dreadful infectious disease and a leading cause of mortality and morbidity worldwide, second in 2020 only to severe acute respiratory syndrome 2 (SARS-Cov-2). With limited therapeutic options available and a rise in multidrug-resistant tuberculosis cases, it is critical to develop antibiotic drugs that display novel mechanisms of action. Bioactivity-guided fractionation employing an Alamar blue assay for Mycobacterium tuberculosis strain H37Rv led to the isolation of duryne (13) from a marine sponge Petrosia sp. sampled in the Solomon Islands. Additionally, five new strongylophorine meroditerpene analogues (1-5) along with six known strongylophorines (6-12) were isolated from the bioactive fraction and characterized using MS and NMR spectroscopy, although only 13 exhibited antitubercular activity.

New Bioactive Polyacetylenes from the Marine Sponge Petrosia sp.

Three new polyacetylenes, pellynols P (1), Q (2), and R (3) were isolated from the marine sponge Petrosia sp., along with the known compound pellynol H (4). Their structures were determined by analyses of extensive NMR, HR-MS, and ESI-MS/MS data. All compounds displayed potent cytotoxicities against human hepatocellular carcinoma HepG2, human melanoma A375, and human colorectal carcinoma HT29 cell lines with IC50 values at the range of 1.4-4.4 µM.

A New Tetracyclic Bromopyrrole-Imidazole Derivative through Direct Chemical Diversification of Substances Present in Natural Product Extract from Marine Sponge Petrosia (Strongylophora) sp.

Chemical diversification of substances present in natural product extracts can lead to a number of natural product-like compounds with a better chance of desirable bioactivities. The aim of this work was to discover unprecedented chemical conversion and produce new compounds through a one-step reaction of substances present in the extracts of marine sponges. In this report, a new unnatural tetracyclic bromopyrrole-imidazole derivative, rac-6-OEt-cylindradine A (1), was created from a chemically diversified extract of the sponge Petrosia (Strongylophora) sp. We also confirmed that 1 originated from naturally occurring (-)-cylindradine A (2) via a new reaction pattern. Moreover, (-)-dibromophakellin (3) and 4,5-dibromopyrrole-2-carboxylic acid (4), as well as 2, were reported herein for the first time in this genus. Studies on the possible reaction mechanism and bioactivities were also conducted. The results indicate that the direct chemical diversification of substances present in natural product extracts can be a speedy and useful strategy for the discovery of new compounds.

Sterols from Thai Marine Sponge Petrosia (Strongylophora) sp. and Their Cytotoxicity.

Eight new sterols (1-5 and 11-13), together with eight known compounds (6-10 and 14-16) were isolated from marine sponge Petrosia sp. The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis. The cytotoxicity of some compounds against a panel of human cancer cell lines is also reported.

A tetramic acid derivative with protein tyrosine phosphatase 1B inhibitory activity and a new nortriterpene glycoside from the Indonesian marine sponge Petrosia sp.

During the search for protein tyrosine phosphatase 1B (PTP1B) inhibitors from marine organisms, the known tetramic acid derivative, melophlin C (1), was isolated as an active component together with the new nortriterpenoid saponin, sarasinoside S (2), and three homologues: sarasinosides A1 (3), I1 (4), and J (5), from the Indonesian marine sponge Petrosia sp. The structure of 2 was elucidated on the basis of its spectroscopic data. Compound 1 inhibited PTP1B activity with an IC50 value of 14.6µM, while compounds 2-5 were not active at 15.2-16.0µM. This is the first study to report the inhibitory effects of a tetramic acid derivative on PTP1B activity.

The Halicylindramides, Farnesoid X Receptor Antagonizing Depsipeptides from a Petrosia sp. Marine Sponge Collected in Korea.

Three new structurally related depsipeptides, halicylindramides F-H (1-3), and two known halicylindramides were isolated from a Petrosia sp. marine sponge collected off the shore of Youngdeok-Gun, East Sea, Republic of Korea. Their planar structures were elucidated by extensive spectroscopic data analyses including 1D and 2D NMR data as well as MS data. The absolute configurations of halicylindramides F-H (1-3) were determined by Marfey's method in combination with Edman degradation. The absolute configurations at C-4 of the dioxyindolyl alanine (Dioia) residues of halicylindramides G (2) and H (3) were determined as 4S and 4R, respectively, based on ECD spectroscopy. The C-2 configurations of Dioia in 2 and 3 were speculated to both be 2R based on the shared biogenesis of the halicylindramides. Halicylindramides F (1), A (4), and C (5) showed human farnesoid X receptor (hFXR) antagonistic activities, but did not bind directly to hFXR.

Strongylophorines, meroditerpenoids from the marine sponge Petrosia corticata, function as proteasome inhibitors.

Two new strongylophorine derivatives, along with six known strongylophorines, were isolated from the marine sponge Petrosia corticata as proteasome inhibitors. Of these, a hemiacetal mixture of strongylophorines-13/-14 was the strongest inhibitor of the proteasome with an IC50 of 2.1µM.

Six New Polyacetylenic Alcohols from the Marine Sponges Petrosia sp. and Halichondria sp.

Six new polyacetylenic alcohols, termed strongylotriols A and B; pellynols J, K, and L; and isopellynol A, together with three known polyacetylenic alcohols, pellynols A, B, and C were isolated from the marine sponges Petrosia sp., and Halichondria sp. collected in Okinawa, Japan. Their planer structures were determined based on 2D-NMR and mass spectrometric analysis of the degraded products by RuCl3 oxidation. The absolute stereochemistry of isolates was examined by their Mosher's esters. The strongylotriols were found to be optically pure compounds, whereas the pellynols are diastereomeric mixtures at the C-6 position. Proliferation experiments using the HeLa and K562 cell lines suggested that the essential structural units for activity are the "hexa-2,4-diyn-1,6-diol" and "pent-1-en-4-yn-3-ol" on the termini.

Halenaquinone inhibits RANKL-induced osteoclastogenesis.

Halenaquinone was isolated from the marine sponge Petrosia alfiani as an inhibitor of osteoclastogenic differentiation of murine RAW264 cells. It inhibited the RANKL (receptor activator of nuclear factor-κB ligand)-induced upregulation of TRAP (tartrate-resistant acid phosphatase) activity as well as the formation of multinuclear osteoclasts. In addition, halenaquinone substantially suppressed RANKL-induced IκB degradation and Akt phosphorylation. Thus, these results suggest that halenaquinone inhibits RANKL-induced osteoclastogenesis at least by suppressing the NF-κB and Akt signaling pathways.

Structure elucidation and cytotoxic evaluation of new polyacetylenes from a marine sponge Petrosia sp.

The sponge Petrosia sp. yielded five polyacetylenic compounds (1-5), including two new polyacetylenes, petrosianynes A (1) and B (2). The structures of these compounds were elucidated by detailed spectroscopic analysis and by comparison with the physical and spectral data of related known analogues. Compounds 1-5 exhibited significant cytotoxic activity against a limited panel of cancer cell lines.

Biscembranoids from the marine sponge Petrosia nigricans.

One new biscembranoid, petronigrione (1), and five known compounds, methyl tortuoate B (2), lobophytone U (3), lobophytone H (4), (24S)-ergostane 3beta, 5alpha, 6beta, 25 tetraol-25-monoacetate (5), and (24S)-ergostane-1beta, 3beta, 5alpha, 6beta, 25-pentaol-25-monoacetate (6), were isolated from the methanol extract of the marine sponge Petrosia nigricans. Their structures were established on the basis of spectral and chemical evidence. The cytotoxicity of all compounds was evaluated by MTT assay on four human cancer cell lines, HepG2, KB, LU-1, and MCF-7. Compounds 1 and 2 exhibited moderate cytotoxic activities on the four human cancer cell lines with IC50 values ranging of 20.7 - 28.9 microg/mL.

Identification of chiral alkenyl- and alkynylcarbinols as pharmacophores for potent cytotoxicity.

Illumination by acetylene: Systematic structural variations in a series of archetypal acetylenic lipids derived from the naturally occurring (S,E)-icos-4-en-1-yn-3-ol allowed the discovery of a series of 3R-like 1,4-di-unsaturated carbinol units with a significant and systematic enantiomeric effect on cytotoxicity.

Structures and cytotoxic evaluation of new and known acyclic Ene-Ynes from an American Samoa Petrosia sp. Sponge.

Four new compounds, (-)-petrosynoic acids A-D (1-4), and five known congeners, pellynols A (5), C (6), D (7), F (8), and I (9), were isolated from a Petrosia sp. marine sponge collected in American Samoa. Isolation work was guided by cytotoxicity against human lung cancer cells (H460). The structures of the C31-C33 polyacetylenes (1-9) were determined on the basis of 1D- and 2D-NMR analysis, mass spectrometry, and comparison of specific rotation values. Compounds 1-9 were found to be broadly cytotoxic with limited selectivity for cancer cells, as they were all moderately active against the A2058 (melanoma), H522-T1 (lung), and H460 (lung) human cancer cell lines as well as IMR-90 quiescent human fibroblast cells.

Cytotoxic petrosiacetylenes from the marine sponge Petrosia sp.

A novel petrosiacetylene analog (petrosiacetylene E) has been isolated from the Korean marine sponge Petrosia sp., along with petrosiacetylene A, B and C. Their structures were elucidated on the basis of spectroscopic methods and the stereochemistry of the new compound was determined by using the modified Mosher's method. Petrosiacetylene E showed higher cytotoxicity against five human cancer cell lines than petrosiacetylene A and B, presumably due to the additional hydroxy group located at C-16.

Strongylophorine-8, a pro-electrophilic compound from the marine sponge Petrosia (Strongylophora) corticata, provides neuroprotection through Nrf2/ARE pathway.

Green plant-origin electrophilic compounds are a newly-recognized class of neuroprotective compounds that provide neuroprotection through activation of the Nrf2/ARE pathway. Electrophilic hydroquinones are of particular interest due to their ability to become electrophilic quinones upon auto-oxidation. Although marine organisms frequently produce a variety of electrophilic compounds, the detailed mechanisms of action of these compounds remain unknown. Here, we focused on the neuroprotective effects of strongylophorine-8 (STR8), a para-hydroquinone-type pro-electrophilic compound from the sponge Petrosia (Strongylophora) corticata. STR8 activated the Nrf2/ARE pathway, induced phase 2 enzymes, and increased glutathione, thus protecting neuronal cells from oxidative stress. Microarray analysis indicated that STR8 induced a large number of phase 2 genes, the regulation of which is controlled by the Nrf2/ARE pathway. STR8 is the first example of a neuroprotective pro-electrophilic compound from marine organisms.

(-)-Duryne and its homologues, cytotoxic acetylenes from a marine Sponge Petrosia sp.

Six linear acetylenes, (-)-duryne (1) and (-)-durynes B-F (2-6), were isolated from the marine sponge Petrosia sp. Their structures were elucidated by NMR and tandem FABMS analyses. The positions of the olefinic bonds were confirmed by ozonolysis experiments, and the absolute configurations were determined by the modified Mosher's method. Compound 1 was found to be the enantiomer of duryne, a previously reported sponge metabolite. Compounds 1-6 show cytotoxicity against HeLa cells with IC50 values between 0.08 and 0.50 µM.

Enantioselective total synthesis of (-)- and (+)-petrosin.

The enantioselective total synthesis of (-)- and (+)-petrosin is described. The union of two key segments was executed by Suzuki-Miyaura coupling. The quinolizidine rings were stereoselectively constructed via a diastereoselective Mannich reaction and an aza-Michael reaction. The 16-membered ring was constructed by ring-closing metathesis with the second-generation Grubbs catalyst.

Assignment of the structure of petrocortyne A by mixture syntheses of four candidate stereoisomers.

Two different mixture synthesis routes have been used to make the four stereoisomers of petrocortyne A. A first quick and dirty route provided a mixture of the four isomers in nonselective fashion. Mosher and 2-naphthylmethoxyacetic acid (NMA) ester methods were developed to identify the components, and the mixture was partially resolved on analytical chiral HPLC to give the two pure enantiomers of petrocortyne A and the racemate of its diastereomer. A second fluorous mixture synthesis produced all four isomers of petrocortyne A in individual pure form. Comparison of spectra of Mosher derivatives of the synthetic isomers with two supposedly different natural products showed that both natural samples were instead identical and had the (3S,14S) configuration. Likewise, petrocortynes B, D, and F-H are (3S,14S) and petrocortyne D is (3R,14S). Having access to all possible candidate isomers of both petrocortyne A and its Mosher derivatives provided a secure structure assignment not so much because one of the isomers matched the natural product, but because all of the other isomers did not.

Square-wave anodic-stripping voltammetric determination of Cd, Pb, and Cu in a hydrofluoric acid solution of siliceous spicules of marine sponges (from the Ligurian Sea, Italy, and the Ross Sea, Antarctica).

Square-wave anodic-stripping voltammetry (SWASV) was set up and optimized for simultaneous determination of cadmium, lead, and copper in siliceous spicules of marine sponges, directly in the hydrofluoric acid solution (approximately 0.55 mol L(-1) HF, pH approximately 1.9). A thin mercury-film electrode (TMFE) plated on to an HF-resistant epoxy-impregnated graphite rotating-disc support was used. The optimum experimental conditions, evaluated also in terms of the signal-to-noise ratio, were as follows: deposition potential -1100 mV vs. Ag/AgCl, KCl 3 mol L(-1), deposition time 3-10 min, electrode rotation 3000 rpm, SW scan from -1100 mV to +100 mV, SW pulse amplitude 25 mV, frequency 100 Hz, DeltaE(step) 8 mV, t(step) 100 ms, t(wait) 60 ms, t(delay) 2 ms, t(meas) 3 ms. Under these conditions the metal peak potentials were Cd -654 +/- 1 mV, Pb -458 +/- 1 mV, Cu -198 +/- 1 mV. The electrochemical behaviour was reversible for Pb, quasi-reversible for Cd, and kinetically controlled (possibly following chemical reaction) for Cu. The linearity of the response with concentration was verified up to approximately 4 microg L(-1) for Cd and Pb and approximately 20 microg L(-1) for Cu. The detection limits were 5.8 ng L(-1), 3.6 ng L(-1), and 4.3 ng L(-1) for Cd, Pb, and Cu, respectively, with t(d) = 5 min. The method was applied for determination of the metals in spicules of two specimens of marine sponges (Demosponges) from the Portofino natural reserve (Ligurian Sea, Italy, Petrosia ficiformis) and Terra Nova Bay (Ross Sea, Antarctica, Sphaerotylus antarcticus). The metal contents varied from tens of ng g(-1) to approximately 1 microg g(-1), depending on the metal considered and with significant differences between the two sponge species.

Petrosamine, a potent anticholinesterase pyridoacridine alkaloid from a Thai marine sponge Petrosia n. sp.

Two pyridoacridine alkaloids, including a known petrosamine and a new 2-bromoamphimedine were isolated from a Thai marine sponge Petrosia n. sp. The alkaloids were characterized on the basis of 1D and 2D NMR, MS, and IR spectroscopy. Only petrosamine showed strong acetylcholinesterase inhibitory activity approximately six times higher than that of the reference galanthamine. A computational docking study of petrosamine with the enzyme from the electric eel Torpedo californica (TcAChE) showed the major contribution to the petrosamine-TcAChE interaction to be arising from the quaternary ammonium group of petrosamine.