Semisynthesis and biological evaluation of novel honokiol thioethers against colon cancer cells HCT116 via inhibiting the transcription and expression of YAP protein.

Honokiol, derived from Magnolia officinalis (a traditional Chinese medicine), has been reported to have anticancer activity. Here, a series of novel honokiol thioethers bearing a 1,3,4-oxadiazole moiety were prepared and evaluated for their anticancer activities against three types of digestive system tumor cells. Biological evaluation showed that honokiol derivative 3k exhibited the best antiproliferative activity against HCT116 cells with an IC50 value of 6.1 µmol/L, superior to the reference drug 5-fluorouracil (IC50: 9.63 ± 0.27 µmol/L). The structure-activity relationships (SARs) indicated that the introduction of -(4-NO2)Ph, 3-pyridyl, -(2-F)Ph, -(4-F)Ph, -(3-F)Ph, -(4-Cl)Ph, and -(3-Cl)Ph groups was favorable for enhancing the anticancer activity of the title honokiol thioethers. Further study revealed that honokiol thioether 3k can well inhibit the proliferation of colon cancer cells HCT116, arresting the cells in G1 phase and inducing cell death. Moreover, a preliminary mechanism study indicated that 3k directly inhibits the transcription and expression of YAP protein without activating the Hippo signaling pathway. Thus, honokiol thioether 3k could be deeply developed for the development of honokiol-based anticancer candidates.

Green synthesis of Poria cocos polysaccharides-silver nanoparticles and their applications in food packaging.

To reduce pollution caused by traditional plastic packaging and preparation of silver nanoparticles (AgNPs), this work aims to develop biological macromolecular packaging films with green synthesized AgNPs. In this study, a novel P. cocos polysaccharide (PCP) with a unique monosaccharide composition was extracted from Poria cocos (Schw.) Wolf. Then, this polysaccharide containing 24.68 % rhamnose was used as a stabilizer for the green synthesis of PCP-AgNPs for the first time. PCP-AgNPs exhibited excellent antibacterial activity against P. aeruginosa, E. coli, and S. aureus, with the highest antibacterial activity against E. coli (inhibition zone diameter = 11.14 ± 0.79 mm). Subsequently, PCP-AgNPs/chitosan (CS) film was successfully prepared by incorporating PCP-AgNPs into the CS film solution. Several experiments demonstrated that the addition of this nanomaterial promoted the formation of noncovalent interactions between CS and PCP-AgNPs, resulting in a more regular and denser film. Compared to the CS film and control group, the PCP-AgNPs/CS film significantly maintained the quality indexes of strawberries. Therefore, this composite film successfully extended the shelf life of strawberries. Regarding safety, these packaging films were not cytotoxic toward RAW264.7 cells. In conclusion, the environmentally friendly PCP-AgNPs/CS film has the potential to replace some traditional food packaging materials.

Identification of O-Methyltransferases Potentially Contributing to the Structural Diversity of 2-(2-Phenylethyl)chromones in Agarwood.

2-(2-Phenylethyl)chromones (PECs) are the primary constituents responsible for the promising pharmacological activities and unique fragrance of agarwood. However, the O-methyltransferases (OMTs) involved in the formation of diverse methylated PECs have not been reported. In this study, we identified one Mg2+-dependent caffeoyl-CoA-OMT subfamily enzyme (AsOMT1) and three caffeic acid-OMT subfamily enzymes (AsOMT2-4) from NaCl-treated Aquilaria sinensis calli. AsOMT1 not only converts caffeoyl-CoA to feruloyl-CoA but also performs nonregioselective methylation at either the 6-OH or 7-OH position of 6,7-dihydroxy-PEC. On the other hand, AsOMT2-4 preferentially utilizes PECs as substrates to produce structurally diverse methylated PECs. Additionally, AsOMT2-4 also accepts nonPEC-type substrates such as caffeic acid and apigenin to generate methylated products. Protein structure prediction and site-directed mutagenesis revealed that residues of L313 and I318 in AsOMT3, as well as S292 and F313 in AsOMT4 determine the distinct regioselectivity of these two OMTs toward apigenin. These findings provide important biochemical evidence of the remarkable structural diversity of PECs in agarwood.