Xanthones with multiple roles against diabetes: their synthesis, structure-activity relationship, and mechanism studies.

A four-step synthetic process has been developed to prepare 1,3,5,8-tetrahydroxyxanthone (2a) and its isomer 1,3,7,8-tetrahydroxyxanthone (2b). 25 more xanthones were also synthesized by a modified scheme. Xanthone 2a was identified as the most active inhibitor against both α-glucosidase and aldose reductase (ALR2), with IC50 values of 7.8 ± 0.5 µM and 63.2 ± 0.6 nM, respectively, which was far active than acarbose (35.0 ± 0.1 µM), and a little more active than epalrestat (67.0 ± 3.0 nM). 2a was also confirmed as the most active antioxidant in vitro with EC50 value of 8.9 ± 0.1 µM. Any structural modification including methylation, deletion, and position change of hydroxyl group in 2a will cause an activity loss in inhibitory and antioxidation. By applying a H2 O2 -induced oxidative stress nematode model, it was confirmed that xanthone 2a can be absorbed by Caenorhabditis elegans and is bioavailable to attenuate in vivo oxidative stress, including the effects on lifespan, superoxide dismutase, Catalase, and malondialdehyde. 2a was verified with in vivo hypoglycemic effect and mitigation of embryo malformations in high glucose. All our data support that xanthone 2a behaves triple roles and is a potential agent to treat diabetic mellitus, gestational diabetes mellitus, and diabetic complications.

Fractional Bandwidth up to 24% and Spurious Free SAW Filters on Bulk 15°YX-LiNbO3 Substrates Using Thickness-Modulated IDT Structures.

To cope with ubiquitous wireless connectivity and the increased and faster data delivery in 5G communication, surface acoustic wave (SAW) filters are progressively requiring wider bandwidths. Conventional bulk 15°YX-LiNbO3 substrates with a large coupling coefficient (K2) are attractive for the low-cost mass production of wideband SAW filters, but these generally suffer from spurious responses, limiting their practical application. In this work, a novel and simple SAW configuration is proposed that uses thickness-modulated interdigital transducer (IDT) structures to overcome the limitations set by spurious responses. Different from the conventional design where the thicknesses of the IDT electrodes in the series and parallel resonators generally kept the same, the proposed configuration adopts IDT electrodes of different thicknesses in the series and shunt resonators to suppress or remove unwanted spurious Rayleigh modes from the filter passband. Two different ultra-wideband SAW filter designs employing thickness-modulated IDTs were designed and fabricated to validate the effective suppression of spurious modes. The SAW filters experimentally featured spurious-free responses in the passband as well as a large 3 dB fractional bandwidth (FBW) in the 18.0% and 24.1% ranges and low insertion losses below 1 dB. This work can significantly broaden the range of applications for SAW devices and can open a pathway to commercialize ultra-wideband SAW filters in 5G communication systems.

Incorporation of nitric oxide donor into 1,3-dioxyxanthones leads to synergistic anticancer activity.

Fifty 1,3-dioxyxanthone nitrates (4a ∼ i-n, n = 1-6) were designed and synthesized based on molecular similarity strategy. Incorporation of nitrate into 1,3-dioxyxanthones with electron-donating groups at 6-8 position brought about synergistic anticancer effect. Among them, compound 4g-4 was confirmed the most active agent against HepG-2 cells growth with an IC50 of 0.33 ±â€¯0.06 µM. It dose-dependently increased intramolecular NO levels. This activity was attenuated by either NO scavenger PTIO or mitochondrial aldehyde dehydrogenase (mtADH) inhibitor PCDA. Apoptosis analysis indicated different contributions of early/late apoptosis and necrosis to cell death for different dose of 4g-4. 4g-4 arrested more cells on S phase. Results from Western Blot implied that 4g-4 regulated p53/MDM2 to promote cancer cell apoptosis. All the evidences support that 4g-4 is a promising anti-cancer agent.

Extraction and detailed characterization of phospholipid-enriched oils from six species of edible clams.

Phospholipid (PL)-enriched oils were recovered from six species of edible clams, namely Cyclina sinensis, Mactra chinensis Philippi, Mactra veneriformis Reeve, Meretrix meretrix, Ruditapes phliippinarum and Saxidomus purpurata, using a mixture of ethanol and hexane (1:1, v/v). The oils contained a high proportion of polyunsaturated fatty acids (PUFA) (26.78-45.36% of total FAs), especially eicosapentaenoic acid (EPA) (8.17-10.48% of total FAs) and docosahexaenoic acid (DHA) (7.83-21.34% of total FAs). The oils also contained a high percentage of PL (39.86-74.05% of total lipids). Among PL, phosphatidylcholine (37.40-52.19mol%) and phosphatidylethanolamine (34.74-43.10mol%) were dominant. At least 435, 442, 513, 438, 433 and 437 glycerophospholipid (GP) molecular species were characterized, respectively, in lipids from Cyclina sinensis, Mactra chinensis Philippi, Mactra veneriformis Reeve, Meretrix meretrix, Ruditapes phliippinarum and Saxidomus purpurata. Most of the predominant GP molecular species contained PUFA, mainly EPA and DHA, indicating that clam is a potential resource of PUFA enriched GP.

DMXAA-pyranoxanthone hybrids enhance inhibition activities against human cancer cells with multi-target functions.

Four 5,6-dimethylxanthone-4-acetic acid (D) and pyranoxanthone (P) hybrids (D-P-n) were design-synthesized based on multi-target-addressed strategy. D-P-4 was confirmed as the most active agent against HepG-2 cell line growth with an IC50 of 0.216 ± 0.031 µM. Apoptosis analysis indicated different contributions of early/late apoptosis/necrosis to cell death for both monomers, the combination (D + P in 1:1 mol ratio) and D-P-4. They all arrested more cells on S phase. Western Blot implied that D-P-4 regulated p53/MDM2 to a better healthy state. Moreover, it improved Bax/Bcl-2 signaling pathway to increase cancer cell apoptosis. In all cases studied, D-P-4 showed the best activity and synergistic effect. All the evidences support that D-P-4 is a better anti-cancer therapy with multi-target functions.

Synthesis of xanthone derivatives and studies on the inhibition against cancer cells growth and synergistic combinations of them.

34 Xanthones were synthesized by microwave assisted technique. Their in vitro inhibition activities against five cell lines growth were evaluated. The SAR has been thoroughly discussed. 7-Bromo-1,3-dihydroxy-9H-xanthen-9-one (3-1) was confirmed as the most active agent against MDA-MB-231 cell line growth with an IC50 of 0.46 ± 0.03 µM. Combination of 3-1 and 5,6-dimethylxanthone-4-acetic acid (DMXAA) showed the best synergistic effect. Apoptosis analysis indicated different contributions of early/late apoptosis and necrosis to cell death for both monomers and the combination. Western Blot implied that the combination regulated p53/MDM2 to a better healthy state. Furthermore, 3-1 and DMXAA arrested more cells on G2/M phase; while the combination arrested more cells on S phase. All the evidences support that the 3-1/DMXAA combination is a better anti-cancer therapy.

Characterization of glycerophospholipid molecular species in six species of edible clams by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.

The molecular species of glycerophosphocholine (GPCho), glycerophosphoethanolamine (GPEtn), glycerophosphoserine (GPSer), lysoglycerophosphocholine (LGPCho) and lysoglycerophosphoethanolamine (LGPEtn) from six species of edible clams were characterized by using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. At least 435, 453, 468, 443, 427 and 444 glycerophospholipid (GP) molecular species were characterized, respectively, from Cyclina sinensis, Mactra chinensis Philippi, Mactra veneriformis Reeve, Meretrix meretrix, Ruditapes philippinarum and Saxidomus purpurata. Most of the predominant GP molecular species in clam contained polyunsaturated fatty acids (PUFA), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), indicating that clam is a potential resource of GP enriched PUFA. According to the amount of the major molecular species containing EPA and DHA, Cyclina sinensis was the best fit species for GPCho, Mactra veneriformis Reeve was the best fit species for GPEtn, Mactra chinensis Philippi was the best fit species for GPSer and LGPEtn, and Saxidomus purpurata was the best fit species for LGPCho.