羊脆木树皮的化学成分研究(Ⅰ)

采用硅胶柱色谱、重结晶、高效液相色谱半制备法等方法,对羊脆木(Pittosporum kerrii Craib)树皮的氯仿、甲醇部位进行化学成分研究,分离纯化得7个单体,通过波谱分析鉴定其结构,分别为:β-stigmsterol(1)、β-stigmasterol-3-O-β-D-glucopyranoside(2)、ethyl caffeate(3)、2,6-dimethoxy-1,4-benzoquinone(4)、3-hydroxy-4-methoxybenzoic acid(5)、syringaresinol-4,4′-di-O-β-D-glucoside(6)、3,4,5-trimethoxyphenol-1-O-β-D-glucopyranoside(7),其中4、5为首次从该属中分离得到.细胞毒试验表明氯仿提取物及从其中分离出来的化合物3、4都具有明显的细胞毒活性,对K562细胞的IC50分别为3.7、4.0、3.0μg/mL.     

硒代4-脱氧-4′-去甲表鬼臼毒素衍生物的合成及细胞毒性测定

应用硼氢化钠还原法合成四种硒代鬼臼毒素衍生物。反应条件温和 ,无毒害 ,产率较高。通过红外吸收谱图、核磁谱图和质谱分析与目标产物一致。四种衍生物对卵巢癌细胞HO -8910都具有一定的细胞毒作用 ,并与化合物浓度呈明显正相关。     

Synthetic and biological studies on a cyclopolypeptide of plant origin

Objective： A natural cyclic peptide previously isolated from Citrus medica was synthesized by coupling of tetrapeptide units Boc-Leu-Pro-Trp-Leu-OMe and Boc-Ile-Ala-Ala-Gly-OMe after proper deprotection at carboxyl and amino terminals followed by cyclization of linear octapeptide segment. Methods： Solution phase technique was adopted for the synthesis of cyclooctapeptide-sarcodactylamide. Required tetrapeptide units were prepared by coupling of Boc-protected dipeptides viz. Boc-Leu-Pro-OH and Boc-Ile-Ala-OH with respective dipeptide methyl esters Trp-Leu-OMe and Ala-Gly-OMe. Cyclization of linear octapeptide unit was done by p-nitrophenyl ester method. The structure of synthesized cyclopolypeptide was elucidated by FTIR, ^1H NMR, ^13C NMR, FABMS spectral data and elemental analysis. The newly synthesized peptide was evaluated for dif- ferent pharmacological activities including antimicrobial, anthelmintic and cytotoxic activities. Results： Synthesis of sarcodactylamide was accomplished with 〉78% yield utilizing dicyclohexylcarbodiimide （DCC） as coupling agent. Newly synthesized peptide possessed potent cytotoxic activity against Dalton＇s lymphoma ascites （DLA） and Ehrlich＇s ascites carcinoma （EAC） cell lines, in addition to moderate anthelmintic activity against earthworms Megascoplex konkanensis, Pontoscotex corethruses and Eudrilus sp. Moreover, cyclopolypeptide displayed good antimicrobial activity against pathogenic fungi Candida albicans and Gram-negative bacteria Pseudomonas aeruginosa, in comparison to standard drugs griseofulvin and ciprofloxacin. Conclusion： Solution phase technique employing DCC and triethylamine （TEA） as base proved to be effective for the synthesis of natural cyclooctapeptide. N-methyl morpholine （NMM） was found to be a better base for the cyclization of linear octapeptide unit in comparison to TEA and pyridine.     

溴代香豆素对胃癌细胞的细胞毒活性与致死机制研究

为探究合成化合物溴代香豆素的生物活性,将该化合物作用于胃癌细胞进行了体外研究.本研究分别采用磺酰罗丹明染色法和生长曲线法研究了药物的细胞毒活性和癌细胞的致死过程.以彗星电泳技术和瑞士—吉姆萨染色法观察了化合物对细胞核形态变化和核酸损伤效应,最后以琼脂糖凝胶电泳法检测了药物对细胞总DNA的影响.结果显示,溴代香豆素对胃癌细胞具有显著的细胞毒活性,其IC50为21.56μg/m L.药物对细胞的增殖抑制效应和致死效应都具有显著的时间—剂量依赖性.药物作用癌细胞后可引起细胞核形态变化和染色质凝集断裂,并损伤细胞DNA,在电泳中呈梯度降解状态.结果表明,溴代香豆素对胃癌细胞的生长与增殖具有显著的细胞毒活性,并能诱导胃癌细胞发生凋亡.     

牛乳酪蛋白源ACE抑制肽的稳定性和毒理特性研究

研究目的：创新要点：研究方法：重要结论：酸碱热处理对牛乳酪蛋白源血管紧张素转化酶（ACE）抑制肽的抑制活性、游离氨基、色泽及其毒理特性的影响。在pn9.0-12．0的热处理条件下,牛乳酪蛋白源ACE抑制肽的抑制活性降低,色泽加深。热处理后的ACE抑制肽对Caco-2细胞和ECV-304细胞没有毒性作用。以ACE抑制活性、游离氨基、色差值和细胞存活率为检测指标,研究了酸碱热处理对ACE抑制肽的稳定性和毒理特性影响。高温和碱性热处理能破坏酪蛋白源ACE抑制肽的稳定性（见图1～3）。     

15种吡唑啉类似物对AW1神经细胞毒力测定与活体生物活性比较研究

利用MTT法测定15种吡唑啉类似物对RP-HzVNC-AW1(AW1)细胞的毒力,采用浸渍法测定这些化合物对东亚飞蝗(Locusta migratoria)3龄幼虫的触杀作用,并对其关联性进行比较.结果表明:15种吡唑啉类似物均对AW1细胞有增殖抑制作用,对东亚飞蝗都有触杀作用.结果显示,两类化合物中,1-苯基-3-(2-呋喃基)-5-取代吡唑啉类化合物(Ⅱ类)细胞毒力测定与活体生物活性关联性要好于1-乙酰基-3-(2-呋喃基)-5-取代吡唑啉类化合物(Ⅰ类),其中的Ⅱ5、Ⅱ8、Ⅱ9三种化合物对细胞的抑制率与对东亚飞蝗的校正死亡率均高于50%,抑制率分别为76.82%、75.41%和65.87%,校正死亡率分别为53.84%、52.91%和53.55%,细胞毒力与活体检测关联性很大.     

气味沙雷氏菌蛋白组分分离及其体外抗癌活性

用ＳＤＳ－ＰＡＧＥ对经超声波处理的气味沙雷氏菌全菌体进行分离，切胶分别洗脱，经丙酮沉淀、脱盐处理后得到九个蛋白组分，将九个组分分别用Ｌ９２９，ＱＧＹ肿瘤细胞为靶细胞进行细胞毒性试验（ＭＴＴ），经初步鉴定从此且分具有抗癌细胞活性，组分Ｆ６相对分子质量范围为２８０００－３３０００，其抑制５０％细胞生长的蛋白浓度（ＩＣ５０）；对Ｌ９２９细胞为０．０４６ｍｇ／ｍｌ对ＱＧＹ细胞为０．０１２５０ｍｇ／ｍｌ，活     

十二种醇的结构与细胞毒性关系研究

研究了甲醇、乙醇、丙醇、丁醇、乙二醇、丙二醇和丙三醇的细胞胞毒性,分析了甲醇、乙醇、丙醇和丁醇诱导细胞表达ＨＳＰ６８的浓度与其细胞毒性的关系。     

Mode of action for inorganic arsenic toxicity and carcinogenesis

Inorganic arsenic(iAs) at high doses is a known human carcinogen, inducing tumors of the skin,urinary bladder, and lung. It is also associated with noncancer toxicities. An understanding of the mode of action(MOA) for arsenic-induced effects is needed to develop a scientifically-based risk assessment. To determine an MOA for iAs induced toxicities, it is necessary to understand the metabolism, kinetics, cell transport, and interaction with specific proteins of iAs. Based on in vitro investigations using animal and human cells, studies from animal models,and clinical and epidemiological studies, we have proposed an MOA involving formation of sufficient levels of reactive trivalent metabolites which interact with critical free sulfhydryl groups, leading to cytotoxicity and regenerative cell proliferation. There is a strong correlation between in vitro cytotoxicity([0.1 lmol/L trivalent arsenicals) and the no effect levels in rodents [approximately 1 ppm(1 ppm = 1 mg/L) of water or diet]. In epithelial target tissues, the cytotoxic effects of iAs result in chronic precursor lesions which have the potential for an increased risk of developing cancer. In non-epithelial tissues, noncancer toxicities such as hypertension and atherosclerosis develop. This MOA implies a non-linear, threshold dose–response relationship for both non-cancer and cancer end points of exposure to iAs.     

Hydrothermal synthesis of pyrrhotite (Fex-1S) nanoplates and their antibacterial, cytotoxic activity study

The aim of this study was to synthesize and characterize Fe_(x-1)S 2D-nanostructures with pyrrhotite phase,as well as to explore their biological(antibacterial and cytotoxic)properties,namely the expression of reactive oxygen species(ROS)in the exposure of cells and bacteria.Based on hydrothermal synthesis,the characterization of asprepared 2D-nanostructures was performed by XRD,SEM,EDS,and TEM,in which the single-crystalline pyrrhotite phased Fe_(x-1)S nanoplate morphology was observed.The antibacterial activities of Fe_(x-1)S nanoplates against human pathogenic strains such as Staphylococcus aureus,Escherichia coli,and Enterococcus faecalis were tested.Minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)were determined following the broth microdilution method.Cytotoxicity and expression of intracellular ROS of pyrrhotite nanoplates on Human Gingival Fibroblast(HGF),Human Pulp Cells(HPC)and Human Osteoblast(HBC)were calculated.Cell viability was determined by the MTT method.All experiments were performed of three independent experiments and data were analyzed by Kruskal-Wallis and Mann-Whitney tests,also Pearson′s Correlation was performed.The nanoplates exhibited good bactericidal effect.All types of cells tested showed slight cytotoxicity.It was found that intracellular ROS is produced when cells and bacteria tested are exposed to pyrrhotite nanoplates in presence of both air and peroxide hydrogen.ROS production levels were higher in the bacteria than the cells exposed to these nanoplates.