UVA Assisted 4-Thiothymidine for Cancer Treatment

This article reviews the developments of 4-thiothymidine analogues, assisted with UVA light, as a novel cancer therapy. First, the key points on synthetic chemistry, photochemistry and cellular toxicity of 4-thiothymidine are summarized. As the chemical structure of 4-thiothymidine is very similar to that of its parent thymidine, thus 4-thiothymidine can be readily incorporated into cellular DNA, and with the help of thymidine kinase, much more preferably into cancerous DNA. Unlike thymidine, 4-thiothymdine can absorb strongly in UVA (longer wavelengths of UV) light. Thus UVA-assisted 4-thiothymidine offers an effective cancer treatment. Some underlying mechanisms of action by 4-thiothymidine/UVA and compares this cancer approach with the commonly used photodynamic therapy are discussed. The various interactions between 4-thiothymidine with human serum albumin are introduced. Finally, a short conclusion on the past efforts and a brief prospect for future work in this exciting research field are given

Study on the inhibition to tyrosinase in Xinjiang plants

酪氨酸酶广泛存在于微生物，动植物及人体中，是一种多亚基的含铜的氧化还原酶。酪氨酸酶是合成黑色素的重要酶类，通过改变酪氨酸酶的活性可以控制黑色素生成量，从而对生物体内黑色素水平及相关代谢途径产生影响。 本文以新疆植物为研究对象，从新疆植物中提取了一批对蘑菇酪氨酸酶具有抑制作用的天然活性物质。多种植物都是首次研究，还没有文献报道。在理论上从酶学角度系统阐述了天然活性物质与蘑菇酪氨酸酶的作用机理及其生物活性。 本文经过粗提的植物，再经石油醚，乙酸乙酯，氯仿，正丁醇萃取，得到不同提取层的物质，冻干之后样品进行研究，根据各物质在不同溶剂中的溶解度不同，从而得到有效分离。再对不同有机层的物质进行，进一...Tyrosinase is an important enzyme containing oxido-reductase, existing widely in microorganisms, plants and animals and the human body. Tyrosinase is the key enzyme in organisms about melanin synthesis, controlling melanin content by regulating its activity,thereby affecting the melanin levels in organisms and related metabolic pathway. This paper takes Xinjiang plant as the research object, and...学位：理学硕士院系专业：生命科学学院_生物化学与分子生物学学号：2162012115233

Cloning, Expression and Immunolocalization of Aspartyl Protease Inhibitor Gene of Angiostrongylus cantonensis

广州管圆线虫（Angiostrongyluscantonensis）是一种人畜共患自然疫源性寄生虫，能引起人的嗜酸性粒细胞增多性脑膜炎，也被称为广州管圆线虫病。其中间宿主是软体动物，例如福寿螺、玛瑙螺等，并以啮齿类动物等作为其终宿主。人类是广州管圆线虫的偶然宿主，因误食寄生有广州管圆线虫的第三期幼虫（L3）的福寿螺等而引起广州管圆线虫病。 寄生虫的天冬氨酸蛋白酶抑制剂（aspartylproteaseinhibitor，API）在寄生虫的寄生生活中起着重要的作用，包括寄生虫的营养摄取，组织入侵，免疫逃避，生长发育等等。本论文以广州管圆线虫为研究对象，以API基因作为研究的目的基因，对目的基因...Angiostrongylus cantonensis is a serious zoonoses parasite that causing parasitic, can cause eosinophilicmeningitis, also known as Angiostrongyliasis. its intermediate host is mollusca, such as apple snails, achatina fulica and so on. And parasitic on Glires as its final host. Human is the occasional host of this nematode, can catch theAngiostrongyliasis cantonensis by eating its infectivethird st...学位：理学硕士院系专业：生命科学学院_生物化学与分子生物学学号：2162012115230

The synthesis of triazole derivatives on mushroom tyrosinase and their mechanisms

酪氨酸酶广泛的存在于各生物体内，其产物多巴醌能与氨基酸或者蛋白质聚合黑色素，该酶是合成黑色素的关键酶。然而黑色素的过量合成会引起雀斑、黄褐斑、老年斑等色素沉积性皮肤病，此外研究表明，酪氨酸酶还与帕金森综合症、昆虫蜕皮、果蔬褐变有密切关系。因此，控制酪氨酸酶活性的研究在农业、制药业及化妆品行业有重要开发价值。 4-氨基-3-肼基-5-巯基-1，2，4-三唑（AHMT）为五元氮杂环，是酰胺键的电子等排物，也具有潜在的配位键，而苯甲醛类衍生物为酪氨酸酶底物的类似物，可以竞争性抑制酶失活性。本文以AHMT为母核与苯甲醛衍生物反应，合成了一系列的抑制剂。反应在乙醇溶液中进行，回流3h，抽滤，重结晶，烘...Tyrosinase is the key enzyme for the synthesis of melanin and widely exists in various organisms, the dopaquinone, the product of enzyme, can aggregate melanin with amino acids or proteins. However, excess melanin could cause sedimentary pigment diseases such as, freckles, chloasma, age spots. Besides the tyrosinase is close relationship to parkinson's disease, insect molting and fruit browning. T...学位：理学硕士院系专业：生命科学学院_生物化学与分子生物学学号：2162013115262

Design, synthesis and biological activity evaluation of three types of kinase inhibitors with nitrogen-containing skeletons

蛋白激酶是人类生命活动中重要的信号传递使者，小分子蛋白激酶抑制剂是以蛋白激酶信号通路功能为基础，结合蛋白激酶结构进行设计合成的小分子药物。自2001年，第一个激酶抑制剂类药物Imatinib获得FDA批准，成为本领域发展的里程碑后，小分子激酶抑制剂发展迅速，大量的小分子激酶抑制剂类化合物进入临床使用。在众多蛋白激酶中，RET融合基因被鉴定为NSCLC（非小细胞性肺癌）亚型中的新致癌基因，即RET重排的存在与肺腺癌亚型相关，所以开发针对RET激酶的抑制剂有望用于相关非小细胞肺癌的治疗。 本论文以三类含氮双环母核为基础，以KQF-04-013-01为先导化合物（leadcompound），辅助以...Protein kinase is an important signaling messenger in human life. Small molecule protein kinase inhibitor can be designed on the basis of protein kinase structure. In 2001, Imatinib was the first kinase inhibitor, approved by FDA, serving as a milestone in the field of targeted cancer theraphy. Until now, 32 small molecule kinase inhibitors have been approved by FDA and achieved great success in c...学位：理学硕士院系专业：生命科学学院_生物化学与分子生物学学号：2162014115257

Insecticidal Activity for Benzaldehyde L-Cysteine Schiff Base Combined with Xylosma Wood Vinegar

木醋碱杀虫剂是一种基于木炭副产物木醋液的绿色杀虫剂,是将精馏木醋液、苯甲醛L-半胱氨酸席夫碱、水杨酸按照一定比例配制而成的.以酪氨酸酶筛选模型研究了苯甲醛L-半胱氨酸席夫碱、精馏木醋液、木醋碱杀虫剂对酪氨酸酶的抑制作用,其导致酪氨酸酶活性的半抑制质量浓度(IC50)分别为15,2.53,0.53 mg/m L.探讨了木醋碱杀虫剂对小菜蛾(Plutella xylostella)、棉铃虫(Helicoverpa armigera)、玉米螟(Pyrausta nubilalis)幼虫的杀虫活性,结果表明木醋碱杀虫剂中苯甲醛L-半胱氨酸席夫碱质量浓度达到15 mg/m L时即可对小菜蛾、棉铃虫、玉米螟二龄幼虫达到很好的杀灭效果.急性毒理实验表明木醋碱杀虫剂实际无毒.慢性毒理研究按照3 g/kg给药量连续灌胃3个月,昆明小鼠的肝脏和肾脏并不存在毒理性变化,表明木醋碱杀虫剂没有慢性毒性.综上所述,木醋碱杀虫剂不仅对酪氨酸酶有很好的抑制作用,还对小菜蛾、棉铃虫、玉米螟等常见农业害虫具有较强的毒杀活性,且实际无毒,具有良好的农业应用前景.The wood vinegar was based on by-product in the process of firing Xylosma charcoal.The wood vinegar base insecticide was a new green type insecticide.We mixed the rectificated wood vinegar,benzaldehyde L-cysteine Schiff base and salicylic acid to make the wood vinegar base insecticide proportionally.The inhibition on tyrosinase in screening model of benzaldehyde L-cysteine Schiff base,rectificated wood vinegar and the wood vinegar base insecticide were determined. The half maximal inhibitory concentration( IC50) were 15,2. 53,0. 53 mg/m L,respectively.Additionally,the insecticidal effects on Plutella xylostella,Pyrausta nubilalis and Helicoverpa armigera of wood vinegar base insecticide were investigated.The results showed that the wood vinegar base insecticide could effectively kill the second-stage juveniles of P.xylostella,P. nubilalis and H. armigera. The results showed that the wood vinegar base insecticide had insecticidal effect.The acute toxicological results showed that the wood vinegar base insecticide had no toxicity.In the chronic toxicological experiment,the group was given a gavage of 3 g / kg with the wood vinegar base insecticide in 3 months.We took the liver and kidney in paraffin section and HE staining after executing the Kunming mouse with cervical dislocation method.The results showed that the wood vinegar base insecticide had no chronic toxicity.In conclusion,the wood vinegar base insecticide could not only inhibit the tyrosinase acitivity,but also show good insecticidal effects on P. xylostella,P. nubilalis and H. armigera with low toxicity.The wood vinegar base insecticide had shown good application prospects in agricultural areas.国家自然科学基金(31371857

2种钼簇化合物对酪氨酸酶的抑制作用及对凡纳滨对虾的保鲜效果研究

通过合成2种高核钼簇（NH4）12[Mo36O108（NO）4（H2O）16].33H2O(Mo36)和[Mo36O112（OH2）16（H2bipy）4].28H2O (Mo36-bipy),其对酪氨酸二酚酶活性的抑制作用机理以及对凡纳滨对虾的防黑变保鲜效果进行研究。结果表明Mo36和Mo36-bipy对酪氨酸二酚酶IC50值分别为0.0358 mmol/L和0.0601 mmol/L,Mo36对酪氨酸酶的抑制作用为可逆竞争性抑制,Mo36-bipy对酪氨酸酶的抑制作用为可逆混合性抑制,且Mo36对酪氨酸酶活性的抑制作用效果优于Mo36-bipy。将凡纳滨对虾在4℃环境下贮藏10 d,通过对感官评分、颜色、pH值、TVB-N和菌落总数等指标检测,发现高核钼簇对样品具有一定保鲜效果。其均能适当提升感官分值、L*值,降低pH值与菌落总数。本研究结果为开发一种新型的抗虾体黑变的保鲜剂提供实验基础,并对多金属氧酸盐的应用研究拓展新的研究领域。国家自然科学基金项目(21871110

The study on GCOE modified AZTS-loaded liposomes

艾滋病(AcquiredImmuneDeficiencySyndrome，AIDS)是由人类免疫缺陷病毒(HumanImmunodeficiencyVirus，HIV)感染导致人体免疫机能缺陷而易于发生机会性感染和肿瘤的临床综合征。高效抗逆转录病毒疗法(HighlyActiveAntiretroviralTherapy，HAART)能抑制HIV复制，降低AIDS的发病率和死亡率，但仍存在药物无法彻底清除HIV、难以在HIV病毒贮库中达到有效浓度、长期用药易产生多药耐药等问题。因此，针对HIV贮库开发新的给药系统是当前国际上抗AIDS研究中的一个热点和难点。由于巨噬细胞是HIV病毒贮库中至关重要...Human immunodeficiency virus (HIV) is a lentivirus that causes acquired immunodeficiency syndrome (AIDS), which progressive failure of the immune system allows life-threatening opportunistic infections and malignancies. Although highly active antiretroviral therapy (HAART) is able to inhibit the replication of the HIV , reduce the morbidity and mortality of AIDS, drugs disable eradicating HIV, ins...学位：理学硕士院系专业：药学院_药理学学号：2452009115303

羟基甲氧基苯甲醛在化妆品中起增白作用的研究

采用酶学动力学方法研究2-羟基-4-甲氧基苯甲醛(HMB)对酪氨酸酶的单酚酶和二酚酶活力的抑制效应。结果表明,HMB对酪氨酸酶单酚酶的效应只表现对稳态活力有明显的抑制作用,但对酶作用的迟滞时间没有影响;随着抑制剂浓度增大,单酚酶活力呈指数下降,导致酶活力下降50%的抑制剂浓度(IC50)为0 352mmol·L-1。HMB对二酚酶的抑制作用表现为可逆过程,IC50为0 164mmol·L-1;抑制作用机理研究表明HMB是一种混合型抑制剂,其抑制常数KI和KIS分别为0 131mmol·L-1和0 253mmol·L-1。通过对HMB抑制酪氨酸酶机理的研究,阐明HMB作为化妆品添加剂的增白作用机理