Water-Soluble,Alanine-Modified Fullerene C60 Promotes the Proliferation and Neuronal Differentiation of Neural Stem Cells

As carbon-based nanomaterials, water-soluble C₆₀ derivatives have potential applications in various fields of biomedicine. In this study, a water-soluble fullerene C₆₀ derivative bearing alanine residues (Ala-C₆₀) was synthesized. The effects of Ala-C₆₀ on neural stem cells (NSCs) as seed cells were explored. Ala-C₆₀ can promote the proliferation of NSCs, induce NSCs to differentiate into neurons, and inhibit the migration of NSCs. Most importantly, the Ala-C₆₀ can significantly increase the cell viability of NSCs treated with hydrogen peroxide (H₂O₂). The glutathioneperoxidase (GSH-Px) and superoxide dismutase (SOD) activities and glutathione (GSH) content increased significantly in NSCs treated even by 20 μM Ala-C₆₀. These findings strongly indicate that Ala-C₆₀ has high potential to be applied as a scaffold with NSCs for regeneration in nerve tissue engineering for diseases related to the nervous system.     

Verrucosidin Derivatives from the Deep Sea Cold-Seep-Derived Fungus Penicillium polonicum CS-252

Six novel verrucosidin derivatives, namely, poloncosidins A–F (1–6), together with one known analogue (7), were isolated and identified from the deep-sea-derived fungus Penicillium polonicum CS-252, which was obtained from cold-seep sediments collected in the South China Sea at a depth of 1183 m. Their structures were mainly established on the basis of a detailed interpretation of NMR spectroscopic and mass spectrometric data. The relative and absolute configurations of compounds 1–6 were determined by ECD calculations and a DP4+ probability analysis. Compounds 1–5 represent the first examples of verrucosidins with a 2,5-dihydrofuran ring which is uncommon among the known analogues. These compounds exhibited inhibitory activities against several human and aquatic pathogens with MIC values ranging from 4 to 32 μg/mL.     

Platelet Derivatives and the Immunomodulation of Wound Healing

Besides their primary role in hemostasis, platelets contain a plethora of immunomodulatory molecules that profoundly affect the entire process of wound repair. Therefore, platelet derivatives, such as platelet-rich plasma or platelet lysate, have been widely employed with promising results in the treatment of chronic wounds. Platelet derivatives provide growth factors, cytokines, and chemokines targeting resident and immigrated cells belonging to the innate and adaptive immune system. The recruitment and activation of neutrophils and macrophages is critical for pathogen clearance in the early phase of wound repair. The inflammatory response begins with the release of cytokines, such as TGF-β, aimed at damping excessive inflammation and promoting the regenerative phase of wound healing. Dysregulation of the immune system during the wound healing process leads to persistent inflammation and delayed healing, which ultimately result in chronic wound. In this review, we summarize the role of the different immune cells involved in wound healing, particularly emphasizing the function of platelet and platelet derivatives in orchestrating the immunological response.     

Hydroxylation of Progesterone and Its Derivatives by the Entomopathogenic Strain Isaria farinosa KCh KW1.1

Progesterone biotransformation is worth studying because of the high industrial value of its derivatives. This study investigated the catalytic ability of the entomopathogenic filamentous fungus strain Isaria farinosa KCh KW1.1 to transform progesterone derivatives: 11α-hydroxyprogesterone, 17α-hydroxyprogesterone, 16α,17α-epoxyprogesterone and pregnenolone. In the culture of Isaria farinosa KCh KW1.1, 11α-hydroxyprogesterone was effectively transformed into only one product: 6β,11α-dihydroxyprogesterone. Transformation of 17α-hydroxyprogesterone gave three hydroxy derivatives: 6β,17α-dihydroxyprogesterone, 12β,17α-dihydroxyprogesterone and 6β,12β,17α-trihydroxyprogesterone. Two products: 6β-hydroxy-16α,17α-epoxyprogesterone and 6β,11α-dihydroxy-16α,17α-epoxyprogesterone, were obtained from the 16α,17α-epoxyprogesterone transformation. We isolated two compounds from the biotransformation medium with pregnenolone: 11α-hydroxy-7-oxopregnenolone and 5α,6α-epoxy-3β,11α-dihydroxypregnan-7,20-dione. In this study, we observed only mono- and dihydroxy derivatives of the tested substrates, and the number of obtained products for each biotransformation did not exceed three.     

Sensitivity analysis of nonlinear fractional order control systems with state delay

In this paper, we consider a class of nonlinear fractional order control system with delay in state variable. Existence and uniqueness of solution are shown by using method of steps. The sensitivity of the state and control with respect to the parameters of the system is shown. Finally, analytical results are substantiated by numerical examples.     

P38促细胞分裂蛋白酶活性抑制剂的分子对接及3D-QSAR研究(英文)

运用分子对接方法研究了26个以嘧啶基咪唑环为基底的一系列同源化合物与p38促细胞分裂蛋白酶晶体结构的结合模式。采用比较分子力场分析法(CoMFA)对选取的对接优势构象进行三维定量构效关系(3D-QSAR)研究。建立了3D-QSAR的CoMFA模型,其非交叉验证系数r~2为0.986,交叉验证相关系数q~2为0.755,外部验证的标准偏差(SD为0.13,表明该模型合理、可信,并具有良好的预测能力。有趣的是,配体与活性周围氨基酸残基4个距离之和与其活性之间具有良好的线性关系(R~2=0.752),揭示了配体分子大小及与氨基酸残基结合的紧密程度对化合物的抑制活性起着主要的作用。最后,根据研究总结的规律设计了4个具有潜在高活性的嘧啶基咪唑衍生物。研究结果可为实验工作者合成新药提供理论有意义的理论参考。     

Synthesis and Anti-Cancer Activity of New Pyrazolinyl-Indole Derivatives: Pharmacophoric Interactions and Docking Studies for Identifying New EGFR Inhibitors

Newly designed series of indole-containing pyrazole analogs, pyrazolinylindoles, were synthesized, and their structures were confirmed based on the spectral data of the ¹H NMR, ¹³C NMR, and HR-MS analyses. Preliminary anti-cancer activity testings were carried out by the National Cancer Institute, United States of America (NCI, USA). Compounds HD02, HD05, and HD12 demonstrated remarkable cytotoxic activities against nine categories of cancer types based cell line panels which included leukemia, colon, breast, melanoma, lungs, renal, prostate, CNS, and ovarian cancer cell lines. The highest cytotoxic effects were exhibited by the compounds HD02 [1-(5-(1-H-indol-3-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenylethanone], HD05 [1-(3-(4-chlorophenyl)-5-(1H-indol-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenoxyethanone], and HD12 [(3-(4-chlorophenyl)-5-(1H-indol-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)(pyridin-4-yl)methanone] against some of the 56 types of NCI-based cell lines in different panels. Compound HD05 showed the maximum range of cancer cell growth inhibitions against all categories of the cell lines in all nine panels. On average, in comparison to the referral standard, imatinib, at a dose level of 10 µM, the HD05 showed significant activity against leukemia in the range of 78.76%, as compared to the imatinib at 9% of cancer cells’ growth inhibitions. Molecular docking simulation studies were performed in silico on the epidermal growth factor receptor (EGFR) tyrosine kinase, in order to validate the activity.     

白藜芦醇糖苷类衍生物的设计与合成

以白藜芦醇及其类似物紫檀芪为原料,采用Schmidt成苷法、相转移催化法,分别与溴代糖和乙酰氨基糖反应,得紫檀芪乙酰葡萄糖苷和(E)-5,4'-二叔丁基二甲基硅基-3-(2"-乙酰氨基-3",4",6"-三乙酰葡萄糖二苯乙烯,其结构经红外光谱、核磁共振氢谱和质谱表征.     

Halochromic Behavior and Anticancer Effect of New Synthetic Anthocyanidins Complexed with β-Cyclodextrin Derivatives

Anthocyanidins, the aglycons of anthocyanins, are known, beyond their function in plants, also as compounds with a wide range of biological and pharmacological activities, including cytostatic effect against various cancer cells. The nature and position of the substituents in the flavylium cation is essential for such biological properties, as well as the equilibrium between the multistate of the different chemical species that are generated by the flavylium cation, including quinoidal base, hemiketal, and cis- and trans-chalcones. In this work, eight new flavylium derivatives were synthesized, characterized for confirmation of the structure by FT-IR and 2D-NMR, and investigated in vitro as possible cytostatic compounds against HCT116 and HepG2 cancer cells. The most active two compounds were explored for their halochromic properties that can influence the biological activity and subjected to molecular encapsulation in β-cyclodextrin derivatives in order to increase their solubility in water and bioavailability. The anticancer effect was influenced by the position (6-, 7-, or 8-) of the methoxy group in the β-ring of the methoxy-4′-hydroxy-3′-methoxyflavylium cation, while the study of the halochromic properties revealed the important role played by the chalcone species of the pH-dependent multistate in both the uncomplexed and inclusion complex forms of these anthocyanidins.     

密度泛函理论和从头计算法研究环戊二烯衍生物气态酸度及其取代基效应

用B3LYP／6-311G(2df,p)／／B3LYP／631 G*和MP2／6-311G(d,p)／／B3LYP／6-31 G*方法准确地预测了9个系列的环戊二烯衍生物(R=CN,CF3,CHO,C283,F,SiH3,H,CH3,OH,NH2)的C-H键的酸度。环戊二烯衍生物气态酸度的范围从284.9 kcal／mol (化合物5a)到357.24kcal／mol(化合物7j),分析取代基的电性、数量以及位置的影响得到了9个QSAR方程。这些数据有助于我们设计以及合成一些有机酸,并有助于深刻理解相关反应中环戊二烯衍生物的性质。