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The RNA binding protein Human Antigen R (HuR) has been identified as a main regulator of the innate immune response and its inhibition can lead to beneficial anti-inflammatory effects. To this aim, we previously synthesized a novel class of small molecules named Tanshinone Mimics (TMs) able to interfere with HuR-RNA binding, and that dampen the LPS-induced immune response. Herein, we present a novel series of TMs, encompassing thiophene 3/TM9 and 4/TM10, furan 5/TM11 and 6/TM12, pyrrole 7b/TM13, and pyrazole 8. The furan-containing 5(TM11) showed the greatest inhibitory effect of the series on HuR-RNA complex formation, as suggested by RNA Electromobility Shift Assay and Time-Resolved FRET. Molecular Dynamics Calculation of HuR - 5/TM11 interaction, quantum mechanics approaches and Surface Plasmon Resonance data, all indicates that, within the novel heteroaryl substituents, the furan ring better recapitulates the chemical features of the RNA bound to HuR. Compound 5/TM11 also showed improved aqueous solubility compared to previously reported TMs. Real-time monitoring of cell growth and flow cytometry analyses showed that 5/TM11 preferentially reduced cell proliferation rather than apoptosis in murine macrophages at immunomodulatory doses. We observed its effects on the innate immune response triggered by lipopolysaccharide (LPS) in macrophages, showing that 5/TM11 significantly reduced the expression of proinflammatory cytokines as Cxcl10 and Il1b., (© 2024. The Author(s).)

The maturation of Arabica coffee fruits is influenced by both endogenous and external factors. The stage of fruit maturation affects the chemical composition of the beans, which in turn impacts the quality of the coffee beverage. During maturation, the fruit peel changes colour from green to red (cherry), signalling the optimal harvest time and suggesting high fruit quality. However, the degree of redness can vary, indicating different levels of maturity. This study aimed to explore the variation in soluble sugar accumulation in relation to the redness of coffee fruit tissues. We classified ripe fruits into six ripeness categories based on the intensity of the red colour of the epicarp, measured using a colourimeter. We analysed total soluble sugar, sucrose, and starch in three parts: coat (exocarp + mesocarp), coat juice (obtained by squeezing the coat), and beans. Our findings reveal that the variation in sugar in the endosperm does not correspond to changes in the coat, suggesting separate regulation of sugar accumulation, particularly sucrose, which is crucial for coffee quality. Our data indicate that there is no transfer of sucrose and reducing sugars from the red coat to the bean.