1,3-取代吲唑类低氧诱导因子l抑制剂的设计合成及其抗肝癌活性

低氧诱导因子l（HIF-1）与肿瘤细胞的生长、侵袭和耐药密切相关,在肿瘤细胞内HIF-1高度表达,因此新型的HIF-1抑制剂可作为潜在的抗肿瘤药物。本文合成了9个1,3-取代吲唑衍生物。通过蛋白质印迹（Western Blot）法及实时定量荧光PCR（Real time-PCR）等方法检测了其对HIF-1及其靶基因血管内皮生长因子（VEGF）表达水平的影响,并以3-（5’-羟甲基-2’-呋喃基）-1-苯甲基吲唑（YC-1）为阳性对照药物初步评价了其体外抗肝癌细胞增殖的生物活性。实验发现化合物7b可显著抑制HIF-1及其下游靶基因VEGF的表达,且体外抗肝癌增殖生物活性优于YC-1,半抑制浓度(IC50)值为10.37μmol/L。研究结果表明,3-（5’-羟甲基-2’-呋喃）-1-（1″-对甲苯磺酰基）吲唑具有靶向抑制HIF及良好的抗肝癌活性作用。福建省科技厅项目(2015Y0081,2015J01350);;厦门大学大学生创新创业训练计划项目(2016X0644,20720152005)~

南極ドームふじ基地における第2期氷床深層コア掘削

南極ドームふじ基地において，第2 期氷床深層コア掘削が行われた．2001 年のパイロット孔掘削に引き続き2003/2004 シーズンから4 か年にわたり本格的な深層コア掘削を実施し，2007 年1 月に3035.22 m 深に達した．夏期間のみの掘削としたので，効率よく掘削できるように第1 期深層コア掘削システムの問題点を解決しながら多くの改良を施した．特に1 回の掘削で採取可能なコア長を2.3 m から3.84 m にしたことと切削チップ収納効率を高めたことが大きい．本報告では，現地で使用した掘削システムの概要とともに，掘削の方法，掘削の経過を述べるとともに，掘削中に生じた様々なトラブルについても報告し，併せて今後の課題を示した． The second deep ice coring project was carried out at Dome Fuji, Antarctica. Following the pilot hole drilling in 2001, deep ice core drilling was conducted for four years from the 2003/2004 austral summer season, reaching a depth of 3035.22 m in January 2007. The drilling was performed only in the summer season. Therefore, many improvements were made to the problems of the first deep ice core drilling system to enable efficient drilling. In particular, the core length that can be obtained at one time was increased from 2.3m to 3.84 m, and the chip storage efficiency was enhanced. In this report, the outline of the drilling system, the method of drilling, the progress of drilling operation, and various troubles were reported. Also, future issues are indicated

The Interaction Mechanism Between Paclitaxel and HSA

以人血清白蛋白(HSA)为实验材料,通过荧光光谱、等温滴定量热及紫外-可见吸收光谱等技术研究化疗药物紫杉醇与其的结合机理.荧光光谱检测结果表明:紫杉醇主要通过氢键和范德华力与HSA结合,并引起其内源荧光的猝灭.在温度为303k下,二者间的结合常数为10.7x103 l/MOl.紫外-可见吸收光谱检测发现,随着紫杉醇浓度的增加,HSA在278nM处的吸收峰增大,证明二者结合后HSA的构象发生了改变.等温滴定量热实验则进一步说明二者的结合是一个自发进行的放热反应,在温度为303k下结合常数为8.8x103 l/MOl,焓变、熵变及吉布斯自由能分别为-99.1kJ/MOl,-183.6J/(MOl·k)和-43.5kJ/MOl.本研究为紫杉醇在血液中的运输及传递提供理论支持.The interaction mechanism of chemotherapy drugs paclitaxel with human serum albumin(HSA)was studied using fluorescence spectroscopy,isothermal titration calorimetry,and UV spectroscopy.The result of fluorescence experiment showed that the intrinsic fluorescence of HSA was quenched by the binding of paclitaxel,with an binding constant of 10.7×103 L/mol at 303K,and the main forces were hydrogen bonds and van der Waals forces.The result of UV-visible spectroscopy experiment showed that the absorption peak of HSA at 278nm increased with the increase of concentrations of paclitaxel.Such phenomenon implied that the interaction might lead to the conformation change of HSA.Isothermal titration calorimetry experiment further confirmed that the interaction between HSA and paclitaxel is a spontaneous process of exothermic reaction,of which the binding constant,enthalpy change,entropy,and Gibbs free energy are 8.8×103 L/mol,-9.9kJ/mol,-183.6J/(mol·K)and-19.1kJ/mol,respectively at 303K.Our current study provides a theoretical explanation for processes of transport and delivery of paclitaxel in the blood.中央高校基本科研业务费专项资金项

Synthesis and Antitumor Activities of 4-Substituted Phenoxybenzamide Derivatives

以4-羟基苯甲酸乙酯为原料,经烃化、水解、缩合反应,合成了6个酰胺类衍生物。其结构经核磁共振氢谱、碳谱和高分辨质谱进行了表征,并对人体肿瘤细胞株进行了初步体外抗肿瘤活性评价。结果表明化合物n-(4-氟苯基)-4-苯氧基苯甲酰胺具有良好的抗肿瘤活性。Six amide derivatives were synthesized via4-hydroxybenzoic acid as start material and alkylation,hydrolysis and condensation reactions.The structure was confirmed by1 HNMR,13CNMR and HRMS.The antitumor effect of all thenewly synthesized compounds on the in vitro growth of tumor celllines was evaluated.The results show that the N-(4-fluorophenyl)-4-phenoxybenzamide has good anti-tumor activity.厦门大学中央高校基本科研业务费资助项

Synthesis of Novel 7-Substituted-5-phenyl-[1,2,4]triazolo[1,5-a] Pyrimidines with Anticonvulsant Activity

Considerable interest has been focused on the triazole structure, which has been known to possess a broad spectrum of biological activities such as antitumor, anti-inflammatory, antimicrobial, antiviral, and anticonvulsant activities. Before this, several heterocyclic compounds containing triazole were synthesized that had shown considerable anticonvulsant activity. As part of our continuous research in this area, we have synthesized several new 7-substituted-5-phenyl-[1,2,4] triazolo[1,5-a] pyrimidines (compounds 3a-3i, 5a-5j) through incorporating triazole moiety into the pyrimidine ring, which are expected to have the synergistic effect in dealing with the epilepsy. Their anticonvulsant activities were measured through the Maximal electroshock (MES) test. Carbamazepine and valproate were considered as positive control drugs with anticonvulsant effects [ED50 = 11.8 and 272 mg/Kg]. Amongst the compounds tested, compound 3f, 7-(heptyloxy)-5-phenyl-[1,2,4] triazolo[1,5-a] pyrimidine, showed potent anticonvulsant activity with ED50 84.9 mg/Kg, which was weaker than carbamazepine, but better than valproate.National Natural Science Foundation of China [30860340

Promotion of Capability Building of Control of Invasion of Forcipomyia taiwanna

推動建構小黑蚊防治專案計畫摘要：「小黑蚊防治推廣中心」於2008年9月22日在中興大學昆蟲學系設立，提供小黑蚊防治諮詢服務，洽詢專線電話04-22852473，專屬網站網址www.bitingmidge.org.tw，專用電子信箱為[email protected]。規劃並推動台中縣市、南投縣、花蓮縣、彰化縣、雲林縣、嘉義縣、與台南縣等八縣市27個社區、學校進行小黑蚊防治工作，並於前述縣市進行小黑蚊棲群密度監測調查。累計舉辦17場防治教育宣導講習會，編印防治教育宣導摺頁8000份，完成防治推廣手冊2000本與光碟攝錄、剪輯、配音等工作。收集黑蚊相關學術報告、學位論文、研討會論文、專著及計畫報告計75篇，並進行報告研析。11月6、7日舉辦環保人員小黑蚊防治教育訓練班，縣市環保局及鄉鎮公所環保人員與會43人，41人通過考試，發給證書。11月14日於台中市私立中台科技大學舉辦全國性小黑蚊防治學術研討會「2008小黑蚊發生、生態與防治研討會」，出席人數約300人。Project name:Promotion of Capability Building of Control of Invasion of Forcipomyia taiwanna.Abstract:The “Biting Midge Control and Extension Center” was founded at the Department of Entomology, National Chung Hsing University, Taichung on Sep. 22nd, 2008. Currently, this center provides consultancy services on biting control through website (www.bitingmidge.org.tw), e-mail ([email protected]), and direct phone (04-22852473). Control programs were initiated in 27 communities covering Taichung, Nantou, Hualien Changhua, Yunlin, Chiayi and Tainan counties as well as Taichung City focusing on local biting midge control and density monitoring. Seventeen implementation sessions were held in individual townships to extend basic principles for effective biting midge control. Eight thousand copies brochures were printed and distributed to related parties; and the draft of control manual and a DVD were also prepared for extension purposes. One training workshop was held on 6th and 7th of November with 41 persons from different counties and townships, and all the participants were certified upon completion of the training courses. The nationwide symposium entitled “2008 Symposium on the Occurrence, Ecology and Control of Biting Midge” was held in Central Taichung University of Science and Technology on the 14th of November with nearly 300 participants from government sectors, academic institutions, private companies, etc

Design, synthesis and biological evaluation of B-region modified diarylalkyl amide analogues as novel TRPV1 antagonists

Basic Research Program of the Korea Science; Natural Science Foundation of Fujian Province of China [2011J01257]Design, synthesis and biological evaluation of B-region, known to be a dipolar interacting pharmacophore, modified diarylalkyl amide analogues for novel TRPV1 (transient receptor potential channel, vanilloid subfamily member 1) antagonists was described. A variety of moieties including guanidines, heterocyclic rings, cinnamides, and alpha-substituted acetamides were introduced at the B-region. TRPV1 antagonistic activities of these analogues were evaluated by Ca-45(2+) uptake assay in rat DRG neuron. In particular, alpha,alpha-difluoroamide 53 exhibited 3-fold more potent TRPV1 antagonistic activity (IC50 = 0.058 mu M) than the parent amide analogue 6

Synthesis and Anticonvulsant Activity of 7-Alkoxy-Triazolo-[3, 4-b] Benzo[d]Thiazoles

National Natural Science Foundation of China [30860340]The present study describes the chemical synthesis and anticonvulsant activity evaluation of a series of 7-alkoxy-triazolo-[3, 4-b]benzo[d]thiazoles. Most compounds exhibited good anticonvulsant activity in the Maximal electroshock (MES) test. And the structure-activity relationships (SAR) were analyzed. Among the compounds studied, 7-octyloxy-triazolo-[3, 4-b]benzo[d]thiazole (5g) was found to be the most potent compound with a median effective dose (ED(50)) value of 8.0 mg/kg and a protective index (PI) value of 15.0, possessing better anticonvulsant activity and higher safety than marketed drugs carbamazepine and phenytoin. The mechanism study of compound 5g showed that it displayed broad spectrum activity in several models, and it is likely to have several mechanisms of action (including inhibiting voltage-gated ion channels and GABAergic activity)

Structure-based design, synthesis, and anticonvulsant activity of isatin-1-N-phenylacetamide derivatives

National Natural Science Foundation of China [30960458]; Natural Science Foundation of Zhejiang Province of China [LY12C19005, LY13C200006]; Major Science and Technology Project of Zhejiang Province of China [2012C11015-2]; Public Welfare of Zhejiang Province of China [2012C21068]; Zhejiang Marine Biotechnology Innovation Team (ZMBIT) [2010R50029]In an effort to develop the potent anticonvulsant agents, a series of novel isatin-1-N-phenylacetamide derivatives was synthesized and screened for their in vivo anticonvulsant activity against maximal electroshock test and evaluated for their neurotoxicity by the rotarod test at the same dose levels. Ten compounds exhibited the anticonvulsant activity. 2-(5-Methyl-2,3-dioxoindolin-1-yl)-N-phenylacetamide (4b) was found to be the most potent compound of the series with an ED50 of 91.3 mg/kg, TD50 of > 1,000 mg/kg, a higher protective index (PI = TD50/ED50, > 11) was gained than the reference drug phenobarbital and carbamazepine. The essential structural features responsible for interaction with receptor site are established within a suggested pharmacophore