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Covering: 2011–2021 Marine mollusks, which are well known as rich sources of diverse and biologically active natural products, have attracted significant attention from researchers due to their chemical and pharmacological properties. The occurrence of some of these marine mollusk-derived natural products in their preys, predators, and associated microorganisms has also gained interest in chemical ecology research. Based on previous reviews, herein, we present a comprehensive summary of the recent advances of interesting secondary metabolites from marine mollusks, focusing on their structural features, possible chemo-ecological significance, and promising biological activities, covering the literature from 2011 to 2021. [ABSTRACT FROM AUTHOR]

A new bis-γ-pyrone polypropionate, 4,16-di-epi-onchidiol (1), along with three known related compounds (2–4) were isolated from the marine pulmonate mollusk Onchidium sp. The structure of compound 1 was elucidated by extensive spectroscopic analysis and by comparison the NMR data with its stereoisomers 2–4, whereas its absolute configuration was determined by the combination of X-ray diffraction analysis and TDDFT-ECD calculation. In bioassay, the isolated compounds exhibited broad cytotoxicity against several cancer cell lines with IC50 values ranging from 24.6 to 88.5μM. [ABSTRACT FROM AUTHOR]

Placobranchus ocellatus is well known to produce diverse and complex γ‐pyrone polypropionates. In this study, the chemical investigation of P. ocellatus from the South China Sea led to the discovery and identification of ocellatusones A–D, a series of racemic non‐γ‐pyrone polyketides with novel skeletons, characterized by a bicyclo[3.2.1]octane (1, 2), a bicyclo[3.3.1]nonane (3) or a mesitylene‐substituted dimethylfuran‐3(2H)‐one core (4). Extensive spectroscopic analysis, quantum chemical computation, chemical synthesis, and/or X‐ray diffraction analysis were used to determine the structure and absolute configuration of the new compounds, including each enantiomer of racemic compounds 1–4 after chiral HPLC resolution. An array of new and diversity‐generating rearrangements is proposed to explain the biosynthesis of these unusual compounds based on careful structural analysis and comparison with six known co‐occurring γ‐pyrones (5–10). Furthermore, the successful biomimetic semisynthesis of ocellatusone A (1) confirmed the proposed rearrangement through an unprecedented acid induced cascade reaction. [ABSTRACT FROM AUTHOR]

Phidianidines A and B are two novel marine indole alkaloids bearing an uncommon 1,2,4-oxadiazole ring and exhibiting various biological activities. Our previous research showed that the synthesized phidianidine analogs had the potential to inhibit the activity of protein tyrosine phosphatase 1B (PTP1B), a validated target for Type II diabetes, which indicates that these analogs are worth further structural modification. Therefore, in this paper, a series of phidianidine derivatives were designed and rapidly synthesized with a function-oriented synthesis (FOS) strategy. Their inhibitory effects on PTP1B and T-cell protein tyrosine phosphatase (TCPTP) were evaluated, and several compounds displayed significant inhibitory potency and specific selectivity over PTP1B. The structure-activity relationship (SAR) and molecular docking analyses are also described. [ABSTRACT FROM AUTHOR]

The first and in-depth chemical investigation of the South China Sea soft coral Sinularia scabra has resulted to the isolation of a library of diverse cembrane type diterpenoids, including six new compounds, namely xiguscabrates A and B (1 and 2), xiguscabral A (3), xiguscabrols A and B (4 and 5), and 8- epi -xiguscabrol B (6), and twenty-seven known analogs (7 – 33). Their structures were elucidated by extensive spectroscopic analysis and by the comparison with literature data. In bioassay, several isolates exhibited inhibitory effects on the ConA-induced T lymphocytes and/or LPS-induced B lymphocytes proliferation. Among them, compound 24 showed considerable specific inhibition on B cell proliferation, with IC 50 value of 4.4 μ M and selectivity index (SI) of 10.9. The structure-activity relationship (SAR) of the tested metabolites was analyzed, and the further mechanism study of the specific B-cell targeted immunosuppressive compound 24 on purified CD19+ B cells was also performed to uncover the effects on the function and maturity of B cells, including cytokines production, abnormal activation, antigen presenting capacity and plasma cells formation. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of phidianidine derivatives were synthesized to study anti-inflammatory activity. • Compounds 9a and 22c exhibited excellent anti-inflammatory activity and low toxicity on IL-17A production in PMA and ionomycin-stimulated EL4 cells. • Compound 9a could decrease the STAT3 phosphorylation at Y705 to inhibit IL-17A production in EL-4 cells. • Molecular docking analysis explained our SAR study. Phidianidines A and B are novel marine indole alkaloids with various biological activities. Based on their potential anti-inflammatory properties, a series of phidianidine derivatives were designed, synthesized, and tested for their effects on IL-17A production in PMA/ionomycin-stimulated T -cell-lymphoma EL-4 cells. Compounds 9a and 22c exhibited excellent anti-inflammatory activity and low toxicity, with IC 50 values of 7.7 μM and 5.3 μM for IL-17A production in PMA/ionomycin-stimulated EL-4 cells, respectively. Further mechanistic study showed that 9a could decrease the STAT3 phosphorylation at Y705 to inhibit IL-17A production in EL-4 cells, indicating its ability of preventing the differentiation of Th17 cells and their possible function. This research may give an insight for the discovery of marine indole alkaloid derived anti-inflammatory drug leads for the treatment of T cell-mediated diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] • First synthesis of five Polybrominated Diphenyl Ethers natural products and 30 new derivatives. • Discovery of two compounds 3 and 17 h selectively act on KCNQ1 and KCNQ2 ion channels. • Provide a class of compounds targeting KCNQ1 and KCNQ2 potassium channels. Natural polybrominated diphenyl ethers, often isolated from marine sponges, have been reported to possess various biological activities, such as antibacterial, antioxidant and antidiabetic effects. Via a high throughput screening of our marine natural product library, the polybrominated diphenyl ether 3 was found to display a KCNQ potassium channel activation effect. To obtain more compound 3 related natural products and their derivatives for further bioactivity study, a diversity-oriented synthesis was conducted, leading to the successful synthesis of five polybrominated diphenyl ether natural products (1 – 4 , 6) and 30 new derivatives. Compound 3 was found to preferentially potentiate KCNQ1 potassium channel, whereas 17h relatively activated KCNQ2 potassium channel. The structure–activity relationship was analyzed assisted by molecular docking and 17h was further conducted for its agonistic mechanism study on KCNQ2 channel. This research work may give an insight for the discovery of marine polybrominated diphenyl ether derived new drug leads. [ABSTRACT FROM AUTHOR]

[Display omitted] • This is the first chemical study of Sinularia pedunculata from the South China Sea. • Three new diterpenoids (1 – 3) were isolated from Sinularia pedunculata. • The quantum mechanical (QM)-NMR methods and spectroscopic analyses were applied to determine relative configurations. • A plausible biosynthetic pathway of compounds 1 – 3 was proposed. Three new diterpenoids (1 – 3), along with four known related compounds (4 – 7), were isolated from the South China Sea soft coral Sinularia pedunculata. Their structures were established by extensive spectroscopic analysis and by comparison of the spectral data with those reported in the literature. The relative configuration of the new compounds was established by spectroscopic analyses and quantum mechanical (QM)-NMR methods. [ABSTRACT FROM AUTHOR]

[Display omitted] • New cembranoid derivatives were obtained by diversity-oriented synthetic strategy. • 11 displayed the most promising anti-inflammation activity. • Our SAR study were explained by the molecular docking analysis. • 11 could suppress the mRNA expression level of inflammatory mediators. Eleven novel cembranoid derivatives were designed, synthesized, and evaluated for their inflammation related activities on the basis of our isolated and previously reported anti-inflammatory marine cembranoids. In bioassay, compound 11 displayed the most promising inhibitory effects with IC 50 value of 1.1 μM for the TNF-α inhibitory activity. The further mechanism study of 11 on the inflammatory signaling transduction of RAW264.7 cells was also performed. This research may give an insight for the discovery of marine cembranoid derived anti-inflammatory drug leads. [ABSTRACT FROM AUTHOR]