Aging is related to the lowered overall functioning and increased risk for various age-related diseases in humans. Sonneradon A (SDA), a new compound first extracted from the edible fruits of mangrove Sonneratia apetala, showed remarkable antiaging activity. However, the role of SDA in antiaging remains unclear. In this article, we studied the function of SDA in antiaging by using the animal model Caenorhabditis elegans. Results showed that SDA inhibited production of reactive oxygen species (ROS) by 53%, and reduced the accumulation of aging markers such as lipids and lipofuscins. Moreover, SDA also enhanced the innate immune response to Pseudomonas aeruginosa infection. Genetic analysis of a series of mutants showed that SDA extended the lifespan of the mutants of eat-2 and glp-1. Together, this effect may be related to the enhanced resistance to oxidative stress via mitochondrial and insulin/insulin-like growth factor-1 signaling (IIS) pathways. The results of this study provided new evidence for an antiaging effect of SDA in C. elegans, as well as insights into the implication of antiaging activity of SDA in higher organisms.

A protocol for the synthesis of unsymmetrical ureas bearing 2-pyridyl units has been developed, relying on metal- and column-free one-pot ammonolysis by using a wide range of aryl and alkyl amines, resulting in nearly quantitative conversions. The reaction is not hindered by either donor or acceptor groups on secondary amine rings containing sp²C, sp³C, O, S, and N atoms, as well as diverse functionalities including variant ring strain and chiral substrates, and could be easily scaled up to yield bulk amounts of triazole attaching pyridyl ureas as potential ASK1 inhibitors. Theoretical DFT computational studies were compared to the initial experimental data supporting a plausible mechanism for the process, from which the relative merits of different mechanistic schemes for direct urea formation could be assessed. This reaction initiates through the in situ pyridinolysis of phenyl chloroformate followed by inner molecular rearrangement to phenyl carbamate hydrochloride. On the basis of calculated energies, a pathway involving a concerted mechanism was speculated to be more accessible and may explain how direct aminolysis occurs through benign base catalysis. Such a mechanism is inconsistent with traditional kinetic modelling of zwitterionic intermediates and neutral ortho-pyridinyl isocyanate during the procedure, which is perhaps more likely applicable for similar meta- and para-pyridinyl fragments with intermolecular rearrangements.

The depolymerized products and oligosaccharide fractions from sea cucumber fucosylated glycosaminoglycans (FGs) are promising anticoagulant candidates, and more novel FG-derived oligosaccharides from low-priced sea cucumbers are expected to be obtained. This study isolated 5−12 oligomers (OF1−OF3) with unusual branches from β-eliminative depolymerized products of Colochirus quadrangularis FG (CqFG). Detailed NMR analyses showed that OF1−OF3 consisted of a chondroitin 4,6-sulfates backbone and some sulfated fucosyl branches (FucS), including monosaccharides (α-l-Fuc_2S4S, α-l-Fuc_3S, α-l-Fuc_4S, α-l-Fuc_2S3S4S, and α-l-Fuc_2S) and a disaccharide D-Gal_3S4S-α1,3-l-Fuc_2S4S with the ratio of ~36:35:10:7:3:9, attached to the C-3 position of β-d-GlcA or its derivatives, such as α-l-Δ4,5GlcA and β-d-GlcA-ol. Unusually, α-l-Fuc_3S was the main FucS branch; no α-l-Fuc_3S4S branch was found, and α-l-Fuc_2S3S4S and α-l-Fuc_2S branches were also found in OF1–OF3. The OF2 and OF3 could strongly inhibit the intrinsic and common coagulation pathways. Intrinsic FXase is a target of OF2 and OF3 inhibiting the intrinsic coagulation pathways, and the unusual side chains may increase the intrinsic FXase inhibitory activity. OF2 and OF3 showed negligible bleeding risk, and less bleeding than heparin (HP), low-molecular-weight heparins (LMWHs), and CqFG. These findings support novel FG oligosaccharides with some unusual branches from low-priced sea cucumbers to be prepared as safer anticoagulants.

The increasing challenge of marine biofouling, mainly due to barnacle settlement, necessitates the development of effective antifoulants with minimal environmental toxicity. In this study, fifteen derivatives of brusatol were synthesized and characterized using ¹³C-NMR, ¹H-NMR, and mass spectrometry. All the semi-synthesized compounds obtained using the Multi-Target-Directed Ligand (MTDL) strategy, when evaluated as anti-settlement agents against barnacles, showed promising activity. Compound 3 exhibited the highest anti-settlement capacity, with an EC₅₀ value of 0.1475 μg/mL, an LC₅₀/EC₅₀ ratio of 42.2922 (>15 indicating low toxicity), and a resuscitation rate of 71.11%, while it showed no significant phenotypic differences in the zebrafish embryos after treatment for 48 h. The toxicity screening of zebrafish also demonstrated the low ecotoxicity of the selected compounds. Furthermore, homology modeling of the HSP90 structure was performed based on related protein sequences in barnacles. Subsequently, molecular docking studies were conducted on HSP90 using these newly synthesized derivatives. Molecular docking analyses showed that most activated derivatives displayed low binding energies with HSP90, aligning well with the biological results. They were found to interact with key residues in the binding site, specifically ARG243, TYR101, and LEU73. These computational findings are anticipated to aid in predicting the enzyme targets of the tested inhibitors and their potential interactions, thus facilitating the design of novel antifoulants in future research endeavors.

Quantitative pyrrole protection was achieved through a self-driven pathway by the combinational assistance of solvent water and dissociative weak H ⁺ .