Table of Content

30 September 2019, Volume 28 Issue 9

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Original articles

Synthetic studies toward resveratrol-based natural products polynapstilbenes A and B

Baiyang Jiang, Lingqi Qiu, Jinrong liu, Hanxuan Wang, Suwei Dong

2019, 28(9):  595-604.  DOI: 10.5246/jcps.2019.09.057

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Resveratrol-based natural products have received considerable attention as synthetic targets due to their versatile bioactivities and unique structures. Herein, we disclose our efforts toward the syntheses of polynapstilbenes A and B, which possess[C8-O-C-C-C7]-type dihydrobenzofuran skeleton that is distinctive compared with the other reported resveratrol-derived natural products. Our approach, featuring an acid-catalyzed conjugate addition followed by cyclization of para-quinone methides and phenols, affords two advanced intermediates that represents the dimethyl-protected aglycon of polynapstilbenes A and B.



Synthesis of two substrate mimics of thioesterase in the biosynthesis of cyclic depsipeptide WS9326A

Zhongyi Zhang, Hanxuan Wang, Guiyang Wang, Xueyang Ma, Tan Liu, Tongtong Geng, Xiaoxu Sun, Donghui Yang, Suwei Dong, Ming Ma

2019, 28(9):  605-614.  DOI: 10.5246/jcps.2019.09.058

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WS9326A is a tachykinin receptor antagonist and quorum sensing inhibitor discovered from several Streptomyces strains. The structure of WS9326A features a (Z)-pentenylcinnamoyl moiety attached on a cyclic depsipeptide skeleton, which is biosynthesized by nonribosomal peptide synthetases (NRPS). The regioselective cyclization in the last step of NRPS catalysis, which is proposed to be catalyzed by a thioesterase (TE) domain in the last module, has not been experimentally characterized. We here reportthe synthesis of two substrate mimics (1 and 2) of the TE (WS9326A-TE) in WS9326A biosynthesis, by using Fmoc-based solid-phase peptide synthesis (SPPS) method. Compounds 1 and 2 are new compounds whose structures have been elucidated based on NMR and HRESIMS analyses. The N-terminal cinnamoyl moiety and C-terminal methylated l-Ser moiety in 2 were incorporated under the mild SPPS conditions. Given the isolation difficulties of substrate of WS9326A-TE from the Streptomyces producers of WS9326A, our synthesis of 1 and 2 set the stage for the reconstitution of WS9326A-TE’s catalytic reaction in vitro in the future.



Studies on the structure-activity relationship of caffeate derivatives as neuroprotective agents

Bolin Wu, Yameng Hao, Ying Chen, Qian Liu, Chao Tian, Zhili Zhang, Junyi Liu, Xiaowei Wang

2019, 28(9):  615-626.  DOI: 10.5246/jcps.2019.09.059

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In the present study, novel ester derivatives of CAPE were designed and synthesized as neuroprotective agents. The anti-inflammatory and antioxidant activities of these compounds were evaluated at the cellular level, while the blood-brain barrier (BBB) permeability was predicted by parallel artificial membrane permeability assay (PAMPA). The results revealed that phenolic hydroxyl groups and double bonds in the structure of CAPE had important effects on neuroprotective activities. Accordingly,a preliminary structure-activity relationship was summarized in this paper. In addition, we observed a significant improvement on BBB permeability. These results provided important references for the structural modification and optimization of CAPE in the future.



Combination therapy of cRGD-DOX self-assembled nanoparticles and bevacizumab for breast cancer

Xueling Wang, Yanqin Liang, Yuan Zhang, Bing He, Wenbing Dai, Hua Zhang, Xueqing Wang, Qiang Zhang

2019, 28(9):  627-640.  DOI: 10.5246/jcps.2019.09.060

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The interplay among diverse cell populations in the tumor microenvironment contributes to tumor progression. Targeting to different cell populations might result in improved therapeutic effects on malignant tumors. Integrins high express on many kinds of tumor cells, and VEGF has a strong effect on tumor angiogenesis. Therefore, based on tumor cells and angiogenesis, we fabricated integrin-targeting cRGD-DOX nanoparticles and combined them with the anti-VEGF antibody bevacizumab. We evaluated the antitumor effect of this combination therapy in an integrin-overexpressing MDA-MB-231 tumor model. The cRGD-DOX nanoparticles were effectively uptake by MDA-MB-231 cells and the uptake was related to the expression of integrinin; cRGD-DOX nanoparticles showed less cytotoxic than free DOX; Bevacizumab did not show significant cytotoxicity against MDA-MB-231 cells at concentrations less than 1 mg/mL. The in vivo results showed that bevacizumab could reduce tumor interstitial fluid pressure; the combination of bevacizumab and cRGD-DOX nanoparticles showed enhanced antitumor effects compared with the corresponding single-agent treatments. These findings suggested the combination of angiogenesis antibody and integrin-targeting nanoparticle loaded with a cytotoxic drug was a promising cancer treatment regimen. 



Tunable gold nanostar synthesis with surfactant-free system

Xupeng Yang, Zhenzhen Yang, Lu Zhang, Qi Sun, Xianrong Qi

2019, 28(9):  641-649.  DOI: 10.5246/jcps.2019.09.061

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Gold nanoparticle is an important photothermal conversion material in photothermal imaging and photothermal therapy research. There are diverse gold nanoparticles, including gold nanospheres, gold nanorods, gold nanocages, gold nanoshells and gold nanostars. Among them, gold nanostar (AuNS) possesses more excellent prospective imaging contrast agent for cancer diagnosis than other shapes of gold nanoparticles because of its larger photon interception area and cross section as well asscattering characteristics. The properties of AuNS are susceptible to synthetic methods and conditions. In this study, we presented surfactant-free methods to synthesize AuNS, discussed the relationship of AuNS characterization with the synthetic conditions and tested its photothermal effect. The results indicated that length and number of branches in AuNSs were the main factor for absorption wavelength in photothermal conversion, and the AuNSs could be more precisely controlled by changing the synthesis conditions.



A novel preparation of Panax japonicas with high bioequivalence of ginsenoside Rg3

Xinyu Shen, Xingchen Wang, Caihong Gu, Feng Yan, Bo Pan, Lizeng Gao, Bingchun Yan, Qi Liu, Rong Hu

2019, 28(9):  650-664.  DOI: 10.5246/jcps.2019.09.062

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In the present study, we aimed to prepare Panax japonicus tablets and carry out quality inspection. Panax japonicus tablets were prepared by ultrafine pulverization-wet granulation, and quality inspection was carried out according to Pharmacopoeia regulations. The plasma concentration of animals with self-made Panax japonicus tablets or ginsenoside Rg3 in single-doseintragastric administration was determined by high-performance liquid chromatography (HPLC). The pharmacokinetic parameters and relative bioavailability were calculated by DAS 2.0 software.The quality inspection of self-made Panax japonicus tablets met the requirements of Chinese Pharmacopoeia (2015 edition), and this preparation had high bioequivalence of ginsenoside Rg3. The preparation of Panax japonicus tablets was reasonable and highly qualified. Moreover, this new Panax japonicus preparation showed better profiles in oral absorption and utilization. This study provided evidence for the industrial production and clinical application of Panax japonicus tablets.



Self-assembly of Ophiopogonis polysaccharide-iron (III) complex in aqueous solution and solid state

Chunxia Tan, Yali Wang

2019, 28(9):  665-672.  DOI: 10.5246/jcps.2019.09.063

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Ophiopogonis polysaccharide-iron (III) (OPI) was prepared and characterized in the present study. The optimum condition for preparing OPI was as follows: OP and trisodium citrate were mixed at a weight ratio of 4:1 and reacted in a water bath at 70 °C for 3 h within the pH range of 8.0–8.5. Aggregation morphology or structure of OPI in aqueous solution and solid state was studied by scanning electron microscopy, transmission electron microscopy and small-angle X-ray diffraction. In aqueous solution, OPI could self-assemble into micron vesicles with flower-shaped morphology. Results of X-ray diffraction showed OPI with layered structure. A core-shell model was proposed for OPI.