In attempt to find new anticancer drugs with high efficiency and low toxicity, twenty-four novel nootkatone-based acyl pyrazole derivatives were successfully synthesized using nootkatone as starting material. Structural confirmation of the target compounds was conducted using FT-IR, NMR, and HRMS techniques. The CCK-8 assay was used to evaluate in vitro antiproliferative activity of the target compounds against three cancer cell lines (HepG2, HeLa, SCC-9) and one normal cell line (MIHA). Results revealed that compounds 4j, 4m, 4t, 4u, and 4v exhibited notable antiproliferative activity against all three cancer cell lines. Particularly, compound 4t demonstrated excellent antiproliferative activity against all three cancer cell line (IC50 values of 18.19 μM, 1.53μM, and 13.33 μM, respectively), and minimal cytotoxicity toward normal MIHA cells (IC50 value of 58.47 µM), indicating that it had certain broad-spectrum antiproliferative activity and safety. Concurrently, a three-dimensional quantitative structure-activity relationship (3D-QSAR) study was carried out. Furthermore, to elucidate the potential action mechanism of compound 4t, network pharmacology and molecular docking techniques were employed to analyze its interaction patterns with the F2, HSD11B1, and SOD2. Compound 4t is worthy of further study as a lead compound with anticancer activity.

To explore new types of anticancer drugs, a series of novel nootkatone-derived pyrazole-amide compounds were synthesized by the multi-step reaction using natural product nootkatone as starting material. The structures of the synthesized compounds were confirmed by Fourier-transform infrared, proton nuclear magnetic resonance (1H NMR), carbon-13 NMR, and high-resolution mass spectrometry. In vitro antiproliferative activity of the target compounds against human hepatocellular carcinoma cells (SMMC-7721, Huh7, and HepG2) and human breast cancer cell lines (MCF-7) has been assessed by the Cell Counting Kit-8 method. It was found that compounds 4i, 4q, 4r, and 4t exhibited good antiproliferative activity against all the tested cancer cells, in which compound 4r had the best activity with half-maximal inhibitory concentration values of 26.19, 1.51, 10.63, and 10.43 µM against SMMC-7721, HepG2, Huh7, and MCF-7 cell lines, respectively. Meanwhile, the three-dimensional quantitative structure-activity relationship model with predictive ability was established by the Comparative Molecular Field Analysis method to investigate the relationship between substituents on the target compounds and antiproliferative activity. Furthermore, the possible interaction mode of compound 4r with Survivin protein was probed by molecular docking, and found that compound 4r shared similar binding patterns with that of Survivin protein inhibitors YM155 and NSC80467. The work can bring new inspiration to the exploration of new types of anticancer drugs.

In an attempt to search for new natural product-based antitumor agents, a series of novel thiazolidinone derivatives of dehydroabietic acid-based B ring-fused-thiazole were designed and synthesized. The primary antitumor tests showed that compounds 5 m exhibited almost the best inhibitory activity against the tested cancer cells. The computational study suggested NOTCH1, IGF1R, TLR4, and KDR were the core targets of the title compounds, and the IC50 of SCC9 and Cal27 is strong correlation with the binding ability of TLR4 and compounds.

文章以广西医科大学公共卫生学院为例,首先阐述了卫生检验与检疫专业"实验室安全与管理"课程思政教学的重要性,然后论述了卫生检验与检疫专业"实验室安全与管理"课程思政教学路径,包括贯彻课程思政教学理念、明确课程思政教学目标、整合课程思政教学内容等.

A series of novel menthone derivatives bearing pyrimidine and urea moieties was designed and synthesized to explore more potent natural product-derived antitumor agents. The structures of the target compounds were confirmed by FTIR, NMR, and HRMS. The in vitro antitumor activity was tested by standard methyl thiazolytetrazolium assay and showed that 4i, 4g, 4s, and 4m are the best compounds with IC50 values of 6.04 ± 0.62µM, 3.21 ± 0.67µM, 19.09 ± 0.49µM, and 18.68 ± 1.53µM, against Hela, MGC-803, MCF-7, and A549, respectively. The results of the preliminary action mechanism studies showed that compound 4i, the representative compound, could induce cell apoptosis in Hela cells in a dose-dependent manner and might arrest the cell cycle in the G2/M phase. Furthermore, the results of network pharmacology prediction and Western blot experiments indicated that compound 4i might inhibit Hela cells through inhibit PI3K/Akt/mTOR signaling pathway. The binding modes and the binding sites interactions between compound 4i and the target proteins were predicted preliminarily by the molecular docking method.

为了研究去氢枞酸对PI3K/AKT/mTOR信号通路的抑制能力,本研究利用分子对接技术预测去氢枞酸对通路蛋白的结合能力和结合方式,用蛋白免疫印迹技术验证通路蛋白受抑制程度,用网络服务器进行类药性与药代动力学的模拟。预测结果发现,去氢枞酸对通路蛋白具有一定的结合能力,预测构像的最低结合能最高为-6.16 kcal/mol;蛋白免疫印迹结果显示,在去氢枞酸作用下,PI3K调控亚基p85的表达明显下调,AKT和mTOR的磷酸化被明显抑制,通路下游磷酸化蛋白的表达也被不同程度的抑制;类药性与药代动力学的模拟发现去氢枞酸通过了大部分的检验。总体上看,去氢枞酸可以作为治疗用PI3K/AKT/mTOR信号通路抑制剂的候选化合物。

In an attempt to search for new natural product-based antitumor agents, a series of novel (aryl)methyl-amine derivatives of dehydroabietic acid-based B ring-fused-thiazole were designed and synthesized. The primary bioassay showed that compounds 5r and 5s presented certain inhibitory activity against cancer cells, weak cytotoxic activity against normal cells, and inhibitory activity against PI3K/AKT/mTOR signaling pathway. The binding modes and the binding site interactions between the active compounds and the target proteins were predicted preliminarily by the molecular docking method.

With the continuous development of the social economy, cultural development has become particularly important, and the sports culture industry is an integral part of cultural evolution. In order to evaluate the timeliness of Guangxi-ASEAN national sports culture cooperation, the basic model for the national traditional sports culture industry competitiveness based on the dynamic algorithm (that is, the improved "Diamond model" theory algorithm) is established in this paper combined with the characteristics of the national traditional sports culture industry, and an evaluation indicator system is constructed for evaluating the competitiveness of the national traditional sports culture industry. Through the concentration processing of various data on the cooperation of 10 selected countries of ASEAN with Guangxi, four common factors are extracted. The sports cultures of Indonesia, Thailand, the Philippines, Malaysia, Singapore and Guangxi cooperation are relatively good, while those of Vietnam, Myanmar, Cambodia, Laos, Brunei and other countries are relatively weak.

Varacin C is a promising anticancer agent and possesses acid-promoted and photo-induced DNA-damaging activities. In this study, we synthesized an analog varacin-1 (VCA-1) and examined its anticancer potentials. The results demonstrated that VCA-1 caused dose-dependent apoptotic cell death in cancer cells. Note that this action is independent of p53 status, because VCA-1 induced similar levels of apoptosis in two different panels of cell lines (HCT116 p53- wild-type vs. HCT116 p53-knockout colon cancer cells, and p53-expressing U2OS vs. p53-deficient saos2 osteosarcoma cancer cells). VCA-1-induced apoptosis was found to be mainly via the extrinsic apoptosis pathway involving caspase-8 activation and XIAP reduction. Forced over-expression of XIAP markedly prevented apoptosis, indicating its essential role in VCA-1 induced apoptosis. On the other hand, VCA-1 treatment enhanced intracellular ROS (reactive oxygen species) generation also in a p53-independent manner, and consequently promoted caspase activation. Pretreatment of N-acetyl cysteine (an antioxidant), rather than z-VAD (specific caspase inhibitor), markedly prevented XIAP reduction, suggesting that XIAP reduction may be resulted from oxidative stress. In conclusion, data from this study reveal the essential roles of ROS generation and XIAP reduction in VCA-1-induced apoptosis in cancer cells. VCA-1 may be a novel cancer therapeutic agent, especially in p53-mutant human cancers.

为了制备天然产物基抑菌剂,以去氢枞酸为原料,设计并合成得到20个新型去氢枞酸基B环并噻唑-酰胺化合物(Ⅵa～t).初步探索了合成条件,并利用FTIR、1HNMR、13CNMR和ESI-MS对目标产物进行了结构表征.还测试了化合物对黄瓜枯萎病菌、番茄早疫病菌、苹果轮纹病菌、花生褐斑病菌和小麦赤霉病菌等5种植物病原菌的抑菌活性.初步的生物活性测试表明,在50mg/L质量浓度下,目标产物去氢枞酸基B环并噻唑-苯甲酰胺(Ⅵj)和中间体去氢枞酸基B环并噻唑-胺(Ⅴ)对苹果轮纹病菌的抑制率分别为90.0％和92.4％(活性级别为A级).

In an attempt to search for new natural products-based antifungal agents, a series of novel dehydroabietic acid derivatives bearing a 1,3,4-thiadiazole-thiazolidinone moiety were designed and synthesized. The primary bioassay used showed that at a concentration of \(50\,\upmu \hbox {g}/\hbox {mL}\), the target compounds 3c, 3f, and 3n exhibited excellent antifungal activity (91.3 % inhibition) against Gibberella zeae, which was equivalent to the commercial antifungal drug azoxystrobin (positive control).

α-Campholenic aldehyde (3) was prepared by the epoxidation and catalytic isomerization ofα-pinene.Then,α-campholenic aldehyde-based thiadiazole(5) was prepared by the cyclization reac-tion of α-campholenic aldehyde-based thiosemicarbazone , which was obtained by the reaction of thio-semicarbazide with 3.Eleven novel α-campholenic aldehyde-based thiadiazole-phosphonate compounds (6a~6k) were synthesized by the Mannich-type reaction from 5.The structures were characterized by 1 H NMR, 13 C NMR, IR and ESI-MS.Antifungal activities test showed that 6b had inhibition rate of 60.5%against Physalospora piricola at 50 μg· mL-1 .

以樟脑酸为原料,经过脱水反应制备樟脑酸酐,再与芳酰肼发生N-酰化反应,合成得到10个樟脑酸基双酰肼化合物Ⅲa～Ⅲj.初步探索了合成条件,并利用FTIR、1HNMR、13CNMR和ESI-MS对目标产物进行结构表征.初步的生物活性测试表明,在50 mg/L质量浓度下,部分化合物表现出良好的抑菌活性,其中樟脑酸基烟酰肼Ⅲh对苹果轮纹病菌的抑制率高达96.3％,优于阳性对照嘧菌酯.

In search of new potent bioactive compounds, a series of dehydroabietic acid-based thiadiazole-phosphonate compounds were designed and synthesized by the Mannich-type reaction. All target compounds were characterized by Fourier transform infrared, H-1 nuclear magnetic resonance (NMR), C-13 NMR, P-31 NMR, electrospray ionization-mass spectrometry, and UV-vis spectroscopy. The preliminary bioassay experiments showed that, at the concentration of 50 mu g ml(-1), some of the target compounds exhibited excellent antifungal activity against the five fungi tested, in which several compounds displayed even better antifungal effects than the commercial antifungal drug azoxystrobin, which served as the positive control in this study.

In an attempt to search for natural product-based insecticidal agents, a series of novel dehydroabietic acid derivatives bearing 1,3,4-thiadiazole moiety were designed and synthesized. Their structures were characterized by IR, MS, 1H-NMR, 13C-NMR, and elemental analysis. The insecticidal activities against cotton bollworm (Helicoverpa armigera), corn borer (Ostrinia nubilalis Hübner), and diamondback moth (Plutella xylostella (L.)) were evaluated. The bioassay test showed that some of the target compounds exhibited excellent insecticidal activities at the concentration of 200 µg/ml; compound 3a had the best mortality rate of 90.0 and 80.0 % against H. armigera and O. nubilalis Hübner, respectively.