Petrosamine Revisited. Experimental and Computational Investigation of Solvatochromism, Tautomerism and Free Energy Landscapes of a Pyridoacridinium Quaternary Salt.

Petrosamine (1)-a colored pyridoacridine alkaloid from the Belizean sponge, Petrosia sp., that is also a potent inhibitor of acetylcholine esterase (AChE)-was investigated by spectroscopic and computational methods. Analysis of the petrosamine-free energy landscapes, pKa and tautomerism, revealed an accurate electronic depiction of the molecular structure of 1 as the di-keto form, with a net charge of q = +1, rather than a dication (q = +2) under ambient conditions of isolation-purification. The pronounced solvatochromism (UV-vis) reported for 1, and related analogs were investigated in detail and is best explained by charge delocalization and stabilization of the ground state (HOMO) of 1 rather than an equilibrium of competing tautomers. Refinement of the molecular structure 1 by QM methods complements published computational docking studies to define the contact points in the enzyme active site that may improve the design of new AChE inhibitors based on the pyridoacridine alkaloid molecular skeleton.

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.

Polyethylene microplastics reduce filtration and respiration rates in the Mediterranean sponge Petrosia ficiformis.

Microplastic (MP) pollution represents a distinctive mark of the Anthropocene. Despite the increasing efforts to determine the ecological impacts of MP on marine biodiversity, our understanding of their toxicological effects on invertebrate species is still limited. Despite their key functional roles, sponges (Phylum Porifera) are particularly understudied in MP research. These filter-feeders extract and retain particles from the water column, across a broad size range. In this study, we carried out a laboratory experiment to assess the uptake of MPs (polyethylene, PE) by the Mediterranean sponge Petrosia ficiformis, how MPs influence key biological process after different times of exposure (24h and 72h) and whether they can be subsequently eliminated. MP uptake increased with time of exposure, with 30.6% of the inoculated MP particles found in sponge samples after 72h. MPs impaired filtration and respiration rates and these effects were still evident 72h after sponges had been transferred in uncontaminated water. Our study shows that time of exposure represents a key factor in determining MP toxicity in sponges. In addition, our results suggest that sponges are able to incorporate foreign particles and may thus be a potential bioindicator for MP pollutants.

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.

Secondary Metabolites from the Marine Sponges of the Genus Petrosia: A Literature Review of 43 Years of Research.

Sponges are prolific sources of various natural products that have provided the chemical scaffolds for new drugs. The sponges of the genus Petrosia inhabit various regions and contain a variety of biologically active natural products such as polyacetylenes, sterols, meroterpenoids, and alkaloids. This review aims to provide a comprehensive summary of the chemical structures and biological activities of Petrosia metabolites covering a period of more than four decades (between 1978 and 2020). It is also described in this review that the major groups of metabolites from members of the genus Petrosia differed with latitude. The polyacetylenes were identified to be the most predominant metabolites in Petrosia sponges in temperate regions, while tropical Petrosia species were sources of a greater variety of metabolites, such as meroterpenoids, sterols, polyacetylenes, and alkaloids.

Genetic diversity, connectivity and gene flow along the distribution of the emblematic Atlanto-Mediterranean sponge Petrosia ficiformis (Haplosclerida, Demospongiae).

BACKGROUND: Knowledge about the distribution of the genetic variation of marine species is fundamental to address species conservation and management strategies, especially in scenarios with mass mortalities. In the Mediterranean Sea, Petrosia ficiformis is one of the species most affected by temperature-related diseases. Our study aimed to assess its genetic structure, connectivity, and bottleneck signatures to understand its evolutionary history and to provide information to help design conservation strategies of sessile marine invertebrates. RESULTS: We genotyped 280 individuals from 19 locations across the entire distribution range of P. ficiformis in the Atlanto-Mediterranean region at 10 microsatellite loci. High levels of inbreeding were detected in most locations (especially in the Macaronesia and the Western Mediterranean) and bottleneck signatures were only detected in Mediterranean populations, although not coinciding entirely with those with reported die-offs. We detected strong significant population differentiation, with the Atlantic populations being the most genetically isolated, and show that six clusters explained the genetic structure along the distribution range of this sponge. Although we detected a pattern of isolation by distance in P. ficiformis when all locations were analyzed together, stratified Mantel tests revealed that other factors could be playing a more prominent role than isolation by distance. Indeed, we detected a strong effect of oceanographic barriers impeding the gene flow among certain areas, the strongest one being the Almeria-Oran front, hampering gene flow between the Atlantic Ocean and the Mediterranean Sea. Finally, migration and genetic diversity distribution analyses suggest a Mediterranean origin for the species. CONCLUSIONS: In our study Petrosia ficiformis showed extreme levels of inbreeding and population differentiation, which could all be linked to the poor swimming abilities of the larva. However, the observed moderate migration patterns are highly difficult to reconcile with such poor larval dispersal, and suggest that, although unlikely, dispersal may also be achieved in the gamete phase. Overall, because of the high genetic diversity in the Eastern Mediterranean and frequent mass mortalities in the Western Mediterranean, we suggest that conservation efforts should be carried out specifically in those areas of the Mediterranean to safeguard the genetic diversity of the species.

Activated production of silent metabolites from marine-derived fungus Penicillium citrinum.

As an attempt to utilize of rare earth elements as a novel method to activate the silent genes in fungus, the marine-derived fungus Penicillium citrinum was cultured under ordinary laboratory fermentation conditions in the presence of scandium chloride (ScCl3, 50 µM), and chemical investigation led to the isolation and characterization of three new peptide derivatives (1-3), along with four known pyrrolidine alkaloids (4-7). Those structures were elucidated by spectroscopic data interpretation, as well as chemical reactions. Comparative metabolic profiling of the culture extracts (with/without scandium chloride) indicated that compounds 1-3 scarcely detected in the absence of ScCl3. In addition, the antibacterial and cytotoxic activities of all isolated products were evaluated.

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.

Antichlamydial Dimeric Indole Derivatives from Marine Actinomycete Rubrobacter radiotolerans.

Chlamydiae are widely distributed pathogens of human populations, which can lead to serious reproductive and other health problems. In our search for novel antichlamydial metabolites from marine derived-microorganisms, one new (1) and two known (2, 3) dimeric indole derivatives were isolated from the sponge-derived actinomycete Rubrobacter radiotolerans. The chemical structures of these metabolites were elucidated by NMR spectroscopic data as well as CD calculations. All three metabolites suppressed chlamydial growth in a concentration-dependent manner. Among them, compound 1 exhibited the most effective antichlamydial activity with IC50 values of 46.6 ~ 96.4 µM in the production of infectious progeny. Compounds appeared to target the mid-stage of the chlamydial developmental cycle by interfering with reticular body replication, but not directly inactivating the infectious elementary body.

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.