分子筛在医学领域的应用及作用机制

沸石分子筛由于其特殊的结构特点, 优异的生物活性、生物稳定性及生物相容性, 研究人员对其进行了大量临床应用方面的研究. 研究表明, 分子筛可用作抗肿瘤治疗的佐剂、抗微生物治疗、药物的载体、快速凝血剂、防止血栓制剂等. 本文将阐述分子筛在医学领域的应用进展及发挥作用的相关机制.     

Syntheses and biological evaluation of BE-43547A2 analogues modified at O35 ester and C15-OH sites

Total syntheses of 6 BE-43547A₂ analogues modified at O35 and C15 sites are reported. Late stage oxidation of 15-deoxy-BE-43547A₂ delivered 15-epi-BE-43547A₂, which verified the proposition that the C15 is an active site for late stage oxidation. The N35 and C15-F of analogues 1b and 1d were synthesized. Cellular level tests indicated O35 is a prohibitive site for modification and substitution of the OH at C15 with F or trim of the OH both led to a dramatic loss of activity. Compound 1e showed comparable inhibitory level towards Panc-1?cells, which indicated that the OH at C15 are permissive site for further modifications.     

Aromatic butenolides produced by a soil ascomycete Auxarthron sp. KCB15F070 derived from a volcanic island

LC/MS-based chemical screening of fungal extract fraction library led to identification of three 2,3-aryl substituted furanone metabolites (1–3), including one known butenolide glycoside (1) whose stereochemistry remained unsolved and two new compounds gotjawaside and gotjawalide (2 and 3), from Auxarthron sp. KCB15F070, a fungus isolated from a soil sample of the volcanic island Jeju, Korea. Their planar structures were elucidated by 1D- and 2D-NMR spectroscopic and HRESIMS spectrometric techniques, and the absolute configurations of three compounds were solved using a combination of chemical derivatizations and computational analysis of vibrational circular dichroism (VCD) spectra.     

提高化学师范学生实践与创新能力的实践探索

师范生教育实践和创新能力是教师培养的薄弱环节,为此,西北师范大学化学化工学院通过实施教师教育能力和科研创新能力提升计划等举措,着重加强对学生教学实践和创新能力的培养,主要采用实践环节教学与中学教学实际相结合、专业学习与科研创新有效结合等方法,有效提高了化学师范生的实践与创新能力。     

化学专业拔尖学生实验教学体系的探索与实践

介绍了山东大学化学学科拔尖学生实验教学体系的探索与实践,在实验教学体系、教学内容、教学方法、师资建设四个方面总结了近十年来课程改革及实施成效,探索适应化学拔尖人才培养的实验课程体系和运行机制。     

Synthesis of P-Stereogenic Diarylphosphinamides as Novel Inhibitors of Melanoma

In this paper, the evaluation on the biological activity of an array of P-stereogenic diaryphosphinamides as novel inhibitors of malignant melanoma was presented. Among 20 derivatives being screened, several of them displayed high inhibition rate up to 90% against the B16 melanoma cells at 100 μg/mL. Moreover, one of them displayed high inhibition activity with IC50 value of 5.8 μg/mL. In contrast, a comparative assay showed that all the compounds were almost inactive or showed only very weak inhibition ability against an array of cell lines including HL7702, Bel7402, HT1080, A549 and McF7 cells. The results suggested that the P-stereogenic diaryiphosphinamides may serve as a class of novel lead molecules for further development of new inhibitors for selective inhibition of melanoma.     

CAGW and TAT‐NLS peptides functionalized multitargeting gene delivery system with high transfection efficiency

Gene therapy has attracted much attention in vascular tissue engineering. However, it is still challenging to develop a novel gene carrier with multifunction to overcome the barriers in gene delivery. Herein, the multitargeting gene complexes were developed based on methoxy‐poly(ethylene glycol)‐b‐poly‐(D,L‐lactide‐co‐glycolide) (mPEG‐b‐PLGA), poly(d ,l ‐lactide‐co‐glycolide)‐g‐polyethylenimine‐g‐CAGW (PLGA‐g‐PEI‐g‐CAGW), cell‐penetrating peptide YGRKKRRQRRR (TAT), nuclear localization signals (NLS), and pEGFP‐ZNF580 (pDNA) with the purpose of enhancing the transfection of endothelial cells (ECs). The low cytotoxic multitargeting gene complexes could be easily prepared by adjusting the weight ratio of mPEG‐b‐PLGA and PLGA‐g‐PEI‐g‐CAGW. Meanwhile, CAGW peptide with selectively ECs‐targeting ability and TAT‐NLS peptide sequence with both cell‐penetrating ability and nuclear targeting capacity were simultaneously introduced into gene complexes in order to enable them with the multitargeting function so as to improve their gene delivery capacity. The pDNA loading capacity of these gene complexes was confirmed by agarose gel electrophoresis assay. MTT results demonstrated that the relatively cell viability of the multitargeting gene complexes was higher than those of other groups. These multitargeting gene complexes showed higher internalization and transfection efficiencies than other groups. These results revealed that CAGW and TAT‐NLS peptide sequences benefited for efficient gene delivery. Furthermore, the wound healing assay demonstrated that the multitargeting gene complexes could promote the proliferation and migration of ECs. These results collectively demonstrated that CAGW and TAT‐NLS peptides functionalized gene delivery system could effectively enhance the transfection of ECs, which has great potential in vascular tissue engineering.     

Design,synthesis, cytotoxicity and 3D-QSAR analysis of new 3,6-disubstituted-1,2,4,5-tetrazine derivatives as potential antitumor agents

We synthesized two new series of 3-substituted-6-(2,5-dimethylpyrazol-1-yl)-1,2,4,5-tetrazines and analysed them for a potential role as antitumor agents. Twenty-two compounds were obtained, and four molecular structures were determined by X-ray diffraction analysis. Using flow cytometry and MTT assay, potential action on cell toxicity was determined for each of the compounds for four cancer cell lines. The potency and selectivity demonstrated by these compounds are dependent on the cancer cell line, where the following compounds were found the most promising agents against certain cell lines: compounds 1i and 1j for HL-60 cells, 1a and 1b on HCT116 cells, 1f on Hela cells and 2h on H1975 cells. The action exerted by these compounds is comparable to the well-known cancer treatment drug etoposide and higher than vatalanib. To arrive at the structural requirements for activity on each cell line, a SAR and 3D-QSAR analysis was carried out. From the 3D-QSAR models, steric and electronic features were identified in the aromatic centres, and were key components for cytotoxic activity on HL-60 cell lines. The cytometry results suggest that some tetrazine derivatives induce apoptosis on HCT116 cells.     

两种多光谱高温计无源温区标定方法抗随机误差能力研究

两种多光谱高温计无源温区标定方法,即依据图形相似性原理的标定方法和依据高温计传递函数的标定方法。为验证两种方法的实用性,通过对黑体辐射出度加入不同大小的随机误差模拟不同测量精度的多光谱高温测量系统,对这两种方法的抗干扰能力进行了研究。实验结果证明,依据图形相似原理的标定方法具有强抗随机误差能力,适用于随机误差较大的测量系统。当随机误差很小时,其精度低于依据传递函数的标定方法,但当随机误差增加到一定范围,其精度远高于后者。基于高温计传递函数的标定方法虽在一定的随机误差范围内具有高的外推标定精度,但抗随机误差能力较弱,适用于随机误差小的测量系统。     

应用化学专业实验教学改革与学生科研能力培养的探索

对应用化学专业实验教学改革以及学生科研能力培养进行了探索, 结果表明, 通过改变教学观念、精选实验内容、采用自主学习教学模式、引入教师科研成果、构建综合实验平台, 可以有效提高学生的创新能力和科研能力。