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Marine compounds represent a varied source of new drugs with potential anticancer effects. Among these, sponges, including those belonging to the Irciniidae family, have been demonstrated to exert cytotoxic effects on different human cancer cells. Here, we investigated, for the first time, the therapeutic effect of an extract (referred as iSP) from the sponge, Ircinia ramosa (Porifera, Dictyoceratida, and Irciniidae), on A375 human melanoma cells. We found that iSP impaired A375 melanoma cells proliferation, induced cell death through caspase-dependent apoptosis and arrested cells in the G1 phase of the cell cycle, as demonstrated via both flow cytometry and qPCR analysis. The proapoptotic effect of iSP is associated with increased ROS production and mitochondrial modulation, as observed by using DCF-DHA and mitochondrial probes. In addition, we performed wound healing, invasion and clonogenic assays and found that iSP was able to restrain A375 migration, invasion and clonogenicity. Importantly, we observed that an iSP treatment modulated the expression of the EMT-associated epithelial markers, E-CAD and N-CAD, unveiling the mechanism underlying the effect of iSP in modulating A375 migration and invasion. Collectively, this study provides the first evidence to support the role of Ircinia ramosa sponge extracts as a potential therapeutic resource for the treatment of human melanoma.

Selective cell tagging (SeCT) therapy is a strategy for labeling a targeted cell with certain chemical moieties via a catalytic chemical transformation in order to elicit a therapeutic effect. Herein, we report a cancer therapy based on targeted cell surface tagging with proapoptotic peptides (Ac-GGKLFG-X; X = reactive group) that induce apoptosis when attached to the cell surface. Using either Au-catalyzed amidation or Ru-catalyzed alkylation, these proapoptotic peptides showed excellent therapeutic effects both in vitro and in vivo. In particular, co-treatment with proapoptotic peptide and the carrier–Ru complex significantly and synergistically inhibited tumor growth and prolonged survival rate of tumor-bearing mice after only a single injection. This is the first report of Ru catalyst application in vivo, and this approach could be used in SeCT for cancer therapy., The combination of a proapoptotic peptide with covalent tagging and a carrier-Ru-complex inhibited tumor growth in mice after a single injection.

Two new steroid sulfates 1 and 2 were obtained from a lipophilic extract of an undescribed bryozoan species in the genus Calyptotheca. The structures of compounds 1 and 2 were elucidated by spectroscopic methods and chemical modifications. Steroids 1 and 2 exhibited moderate cytotoxicity at IC50 54 and 30 µM, respectively, against NBT-T2 cells.

Considering the intrinsic toxicities of transition metals, their incorporation into drug therapies must operate at minimal amounts while ensuring adequate catalytic activity within complex biological systems. As a way to address this issue, this study investigates the design of synthetic prodrugs that are not only tuned to be harmless, but can be robustly transformed in vivo to reach therapeutically relevant levels. To accomplish this, retrosynthetic prodrug design highlights the potential of naphthylcombretastatin-based prodrugs, which form highly active cytostatic agents via sequential ring-closing metathesis and aromatization. Structural adjustments will also be done to improve aspects related to catalytic reactivity, intrinsic bioactivity, and hydrolytic stability. The developed prodrug therapy is found to possess excellent anticancer activities in cell-based assays. Furthermore, in vivo activation by intravenously administered glycosylated artificial metalloenzymes can also induce significant reduction of implanted tumor growth in mice., Considering the intrinsic toxicities of transition metals, their incorporation into drug therapies must operate at minimal amounts while ensuring adequate catalytic activity within complex biological systems. This study investigates the design of synthetic prodrugs that not only can be tuned to be harmless, but are robustly transformed in vivo to reach therapeutically relevant levels.

α-Emission radiotherapeutics has potential to be one of most effective cancer therapeutics. Herein, we report a facile synthesis of an 211At-labeled immunoconjugate for use as an α-emission molecular targeting therapy. We synthesized a tetrazine probe modified with closo-decaborate(2-), a prosthetic group that forms a bioavailable stable complex with 211At. Our one-pot three-component double-click labeling method was used to attach decaborate to trastuzumab (anti-HER2 antibody) using decaborate-tetrazine and TCO-aldehyde probes without reducing the antibody binding affinity. Labeling the decaborate-attached trastuzumab with 211At produced in the cyclotron at the RIKEN Nishina Center, at which highly radioactive 211At can be produced, readily furnished the 211At-labeled trastuzumab with a maximum specific activity of 15 MBq μg−1 and retention of the native binding affinity. Intratumor injection of the 211At-labeled trastuzumab in BALB/c nude mice implanted with HER2-expressing epidermoid cancer cells yielded efficient accumulation at the targeted tumor site as well as effective suppression of tumor growth.

Marine angiosperms produce a wide variety of secondary metabolites with unique structural features that have the potential to be developed as effective and potent drugs for various diseases. Recently, research trends in secondary metabolites have led to drug discovery with an emphasis on their pharmacological activity. Among marine angiosperms, seagrasses have been utilized for a variety of remedial purposes, such as treating fevers, mental disorders, wounds, skin diseases, muscle pain, and stomach problems. Hence, it is essential to study their bioactive metabolites, medical properties, and underlying mechanisms when considering their pharmacological activity. However, there is a scarcity of studies on the compilation of existing work on their pharmacological uses, pharmacological pathways, and bioactive compounds. This review aims to compile the pharmacological activities of numerous seagrass species, their secondary metabolites, pharmacological properties, and mechanism of action. In conclusion, this review highlights the potency of seagrasses as a promising source of natural therapeutical products for preventing or inhibiting human diseases.

Cytotoxic anticancer drugs used in chemotherapy are often antiproliferative agents that preferentially kill rapidly growing cancer cells. Their mechanism relies mainly on the enhanced proliferation rate of cancer cells and is not genuinely selective for cancer cells. Therefore, these drugs can also significantly affect healthy cells. Prodrug therapy provides an alternative approach using a less cytotoxic form of anticancer drug. It involves the synthesis of inactive drug derivatives which are converted to an active form inside the body and, preferably, only at the site of cancerous tissues, thereby reducing adverse drug reaction (ADR) events. Herein, we demonstrate a prodrug activation strategy by utilizing the reaction between aryl azide and endogenous acrolein. Since acrolein is generally overproduced by most cancer cells, we anticipate our strategy as a starting point for further applications in mouse models with various cancers. Furthermore, cancer drugs that have had therapeutic index challenges might be reconsidered for application by utilizing our strategy.

Two new steroid sulfates

Extracts of the sponge Hyattella aff. intestinalis showed moderate inhibition against adenovirus. Chromatographic separation of the extracts followed by analysis of spectroscopic data allowed us to elucidate the structures of three new metabolites as 2α-hydroxyspongia-13(16),14-diene-3-one (4), 3β-hydroxyspongia-13(16),14-diene-2-one (7), and 2α,3α-diacetoxy-17,19-dihydroxyspongia-13(16),14-diene (8) and to identify six known ones 1-3, 5, 6 and 9. Among the molecules, compounds 1 and 3 showed antiviral activity at IC50 17.0 and 52.0 µM.

Natural glycoconjugates that form glycocalyx play important roles in various biological processes based on cell surface recognition through pattern recognition mechanisms. This work represents a new synthesis-based screening strategy to efficiently target the cancer cells by higher-order glycan pattern recognition in both cells and intact animals (mice). The use of the very fast, selective, and effective RIKEN click reaction (6π-azaelectrocyclization of unsaturated imines) allows to synthesize and screen various structurally well-defined glycoalbumins containing two and eventually four different N-glycan structures in a very short time. The importance of glycan pattern recognition is exemplified in both cell- and mouse-based experiments. The use of pattern recognition mechanisms for cell targeting represents a novel and promising strategy for the development of diagnostic, prophylactic, and therapeutic agents for various diseases including cancers.

Chemical analysis of the sponge Dysidea cf. arenaria from Irabu Island provided four new diterpenes 1-4. Their structures were elucidated by NMR and other spectroscopic analyses. All the metabolites retained the spongian skeleton and an isovalerate ester, but were different from those previously isolated from a specimen of Okinawa Island, implying geographic variation. The cytotoxicity of compounds 1-4 to NBT-T2 cells was evaluated and their IC50 values were 3.1, 1.9, 8.4, and 3.1 µM, respectively.

Radiolabeled biomolecules with short half-life times are of increasing importance for positron emission tomography (PET) imaging studies. Herein, we demonstrate an improved and generalized method for synthesizing a [radiometal]-unsaturated aldehyde as a lysine-labeling probe that can be easily conjugated into various biomolecules through the RIKEN click reaction. As a case study, 68 Ga-PET imaging of U87MG xenografted mice is demonstrated by using the 68 Ga-DOTA-RGDyK peptide, which is selective to αV β3 integrins.

Extracts of the sponge Hyattella aff. intestinalis showed moderate inhibition against adenovirus. Chromatographic separation of the extracts followed by analysis of spectroscopic data allowed us to elucidate the structures of three new metabolites as 2α-hydroxyspongia-13(16),14-diene-3-one (4), 3β-hydroxyspongia-13(16),14-diene-2-one (7), and 2α,3α-diacetoxy-17,19-dihydroxyspongia-13(16),14-diene (8) and to identify six known ones 1-3, 5, 6 and 9. Among the molecules, compounds 1 and 3 showed antiviral activity at IC

The secondary metabolites of Xylaria cf. cubensis SWUF08-86 fungus were investigated, and the chromatographic separation of the crude extracts yielded seventeen compounds. The structure elucidation by spectroscopic analysis including 1D and 2D NMR and the comparison of these data with literature, along with HREIMS spectrometry, revealed one new amino amidine derivative (1), together with five known simple cyclic dipeptide analogs, diketopiperazines (2–6) and eleven other known compounds, including one hemi-cycline (10), three aromatic derivatives (11–13), one sesquiterpene (14) and three sterols (15–17). The isolated compounds were screened for anticancer and anti-pathogenic bacterial and fungal activities. Based on this work, Xylaria cf. cubensis SWUF08-86 has proven to be a diverse secondary metabolites producer.

Chemical analysis of the sponge Dysidea cf. arenaria from Irabu Island provided four new diterpenes 1-4. Their structures were elucidated by NMR and other spectroscopic analyses. All the metabolites retained the spongian skeleton and an isovalerate ester, but were different from those previously isolated from a specimen of Okinawa Island, implying geographic variation. The cytotoxicity of compounds 1-4 to NBT-T2 cells was evaluated and their IC50 values were 3.1, 1.9, 8.4, and 3.1 µM, respectively.

Chemical analysis of the sponge Dysidea cf. arenaria from Irabu Island provided four new diterpenes 1-4. Their structures were elucidated by NMR and other spectroscopic analyses. All the metabolites retained the spongian skeleton and an isovalerate ester, but were different from those previously isolated from a specimen of Okinawa Island, implying geographic variation. The cytotoxicity of compounds 1-4 to NBT-T2 cells was evaluated and their IC50 values were 3.1, 1.9, 8.4, and 3.1 µM, respectively.

Two new sesterterpenoids, 1 and 2, were isolated from the sponge Luffariella variabilis. Their planar structures were characterized with spectroscopic analyses. The sole chiral center of compound 1 was elucidated as 12R by comparing observed and calculated optical rotation values. The configurations of compound 2 were determined by NMR and electronic circular dichroism (ECD) studies. Furthermore, compound 2 showed cytotoxicity at IC50 1.0 µM against NBT-T2 cells.

Two isospongian diterpenes 3 and 4 in addition to known metabolites, cacofurans A (1) and B (2), were isolated from a specimen of the sponge Luffariella sp. The structures of 3 and 4 were elucidated by analyzing spectral data and chemical conversions. Although compound 3 has been reported as a synthetic entity, it was found in nature for the first time. Compound 3 showed moderate cytotoxicity.

In the course of our study on the chemical and genetic diversity of the nudibranch Phylidiella pustulosa, we identified a series of isocyanosesquiterpenes. In addition to known sesquiterpenes, we isolated a new molecule 1, the structure of which was elucidated by analyzing NMR and other spectral data. We report the structure and cytotoxicity of compound 1 herein.