曾苏
(1) 手性药物分析; (2) 药物在生物体内转运与代谢; (3) 转基因细胞系的建立及其应用; (4) 药物质量控制。
个性化签名
- 姓名:曾苏
- 目前身份:
- 担任导师情况:
- 学位:
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学术头衔:
博士生导师
- 职称:-
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学科领域:
中药学
- 研究兴趣:(1) 手性药物分析; (2) 药物在生物体内转运与代谢; (3) 转基因细胞系的建立及其应用; (4) 药物质量控制。
邓辉舫(DENG, Huifang),英籍华人,教授,博士生导师,教育部认证的高层次海外留学人才,1957年10月出生于湖南。分别于1981年及1985年在中国获得理学学士及理学硕士学位,于2000年在英国伦敦大学学院(UCL)获得理学博士学位。博士论文是2D液晶显示(LCD)系统关键技术研究(计算机模拟by有限元方法)。
由于他在理论凝聚态(理论物理)方面的出色研究,于1987年被破格提升为副教授,是年29岁。从1989年1月起,在英国学习,工作与生活。
从2001年1月到2004年9月,作为首席科学家及技术总监受聘于英国硅谷-剑桥一家高科技工程软件公司。以其深厚的数学功底及超常的算法分析能力使公司产品的功能及性能跃升到了一个至高的新层次,曾3次获得公司总裁颁发的杰出表现奖。
2004年9月,辞职受聘回国担任华南理工大学国家示范性软件学院院长。现为华南理工大学计算机科学与工程学院教授,博士生导师,先进计算、服务计算与科学计算团队负责人。
发表论文:
到目前为止共发表论文60多篇,其中近40篇在国外刊物上发表,7篇在国际一流刊物上发表(美国物理评论B (Phys. Rev. B)5篇,IEEE Trans 2篇),30篇被SCI,EI,ISTP索引,单篇最高引用次数为 16次。
科研项目:
在英国共主持大中型项目6项。其中包括欧共体项目:Predictive 3D micro-model simulation for Monitor LCDs。
回国后(2004.9)所进行的科研项目:1)用户状态管理子系统开发(企业) ;2)2006年广东省科技厅粤港关键领域重点突破招标立项:“无线射频识别(RFID)物流通关公共服务平台关键技术”(项目编号2006A15006003);3)2006年国家“863”先进制造技术领域RFID技术与应用重点项目:“面向物流应用的电子标签(RFID)服务系统研究”(课题编号:2006AA04A120);4)2007年教育部资助直属高校聘请外籍教师重点项目。
社会兼职:
英国剑桥旭日软件公司客座首席科学家;亚太地区ICT年度大奖赛特邀独立国际评委;2008年度《国家自然科学奖》特邀评审专家(英文组);2006年度863计划信息领域虚拟现实专题课题评议专家;2006年度和2008年度863计划信息技术领域智能感知与先进计算技术专题课题评议专家;IFITA2009 - 国际信息技术与应用论坛)审稿专家组成员;(美国) 国际制造技术与管理杂志(IJMTM)审稿人;广东省企业管理现代化成果评审委员会委员;粤港RFID产业联盟副主席;【大型文献馆藏传书】《当代湖南人-杰出人物篇》编纂委员会委员,并被录入该传书《杰出人物篇》;《中国科技论文在线》特聘评审专家。
个人主页:http://202.38.194.240:8180/CSWeb/showTeacher.html?id=48
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主页访问
8221
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成果阅读
533
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成果数
10
曾苏, Su Zeng, Yao Zu Chen, Liwu Fu, Korey R. Johnson, and Weimin Fan
Clinical Cancer Research Vol. 6, 3766-3773, September 2000,-0001,():
-1年11月30日
Docetaxel, a novel member of the taxoid family, has shown greater potency than paclitaxel in the treatment of advanced breast cancer and certain other solid tumors. The promising clinical activity of docetaxel has also promoted considerable interest in combining this drug with other antitumor agents. In this study, we assessed the cytotoxic interaction between docetaxel and doxorubicin administered at various schedules to human breast and ovarian cancer cells. Through a series of in vitro assays including DNA fragmentation analyses, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, and flow cytometric analyses, we found that the antagonistic interaction occurred when tumor cells were exposed to the two drugs simultaneously or exposed to doxorubicin before docetaxel. However, no antagonism was observed when docetaxel was added before doxorubicin. Further analyses demonstrated that doxorubicin could interfere with the cytotoxic effect of docetaxel on both mitotic arrest and apoptotic cell death. In addition, biochemical examinations revealed that docetaxel could induce phosphorylation of both bcl-2 and c-raf-1, but these changes were inhibited when tumor cells were pretreated or simultaneously treated with doxorubicin. These results indicate that the interaction between docetaxel and doxorubicin is highly schedule dependent. Exposure of tumor cells to doxorubicin before docetaxel could result in pronounced antagonism. The optimal schedule for this combination might be sequential exposure to docetaxel followed by doxorubicin.
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【期刊论文】Establishment of a P-glycoprotein substrate screening model and its preliminary application
曾苏, Yi Wang, Jiang Cao, Su Zeng
World J Gastroenterol 2004; 10(9):1365-1368,-0001,():
-1年11月30日
AIM: To establish a high P-glycoprotein (P-gp) expressing cell line as a model for studying drug absorption and distribution, and to explore the preliminary application of this screening model. METHODS: A full-length MDR1 cDNA fragment in plasmid pMDRA1 was first subcloned into plasmid pET28a(+), then MDR1 cDNA was cut from the recombinant plasmid with double-digestion and ligated into the mammalian expression vector pcDNA3.1(+). The recombinant plasmid pcDNA3.1 (+)/MDR1 was transfected into breast cancer cell line Bcap37 using the Superfect transfection reagent. Several stably transfected clones were obtained after selection with G418. Real-time fluorescent quantitative RT-PCR and Western blot methods were used to detect the expression of P-gp, and the cellular location of the expressed protein was determined by immunohistochemical staining. Drug sensitivity assay was used to evaluate the biological function of expressed P-gp. Concentration of quercetin in cells was determined by highperformance liquid chromatography (HPLC). RESULTS: The recombinant plasmid was confirmed to be inserted in the correct orientation by restrictive enzyme digestion and DNA sequencing. Real-time fluorescent quantitative RT-PCR showed a higher level of P-gp mRNA in transfected cells compared to that in the control cells, and the Western blot result also indicated that P-gp expression in transfected cells was higher than that in control cells. The immunohistochemical staining showed that the expressed P-gp was localized on cell membranes. Drug sensitivity assay showed that the IC50 for adriamycin and colchicine of the transfected cells was higher than that of the control cells. The concentration of quercetin in model cells was lower than that in control cells by HPLC. After P-gp inhibitor verapamil was administered, the concentration of quercetin in model cells was increased. CONCLUSION: A high P-gp expressing cell line can be established, which could provide a suitable in vitro model system for studying drug intestinal absorption mechanism, predicting the drug permeability characteristics and screening new multi-drug resistance reversing agents. With this model, quercetin can be found to be transported by P-gp, and it is a P-gp substrate.
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曾苏, Q. Zhou a, b, T.W. Yaoa, S. Zeng a, *
J. Biochem. Biophys. Methods 54(2002)369-376,-0001,():
-1年11月30日
An enantioselective assay for S-(-)-and R-(+)-propranolol in transgenic Chinese hamster CHL cell lines, expressing human cytochrome P450 (CYP), was developed. The method involves extraction of propranolol from the S9 incubates, using S-(+)-propafenone as internal standard, chiral derivatization with 2,3,4,6-tetra-O-h-D-glucopranosyl isothiocyanate and quantitation by reversed phase high-performance liquid chromatography system with UV detection (k=220nm). A baseline separation of propranolol enantiomers was achieved on a 5-Am reverse-phase ODS column, with a mixture of methanol/water/glacial acetic acid (67:33:0.05, v/v) as mobile phase. The assay is linear from 5 to 500 AM for each enantiomer. The analytical method affords average recoveries of 99.2% and 98.8% for S-(-)-and R-(+)-propranolol, respectively. The limit of quantitation for the method is 5 AM for both S-(-)-and R-(+)-propranolol. The reproducibility of the assay is satisfactory (RSD<10%). The method allowed study of the depletion of S-(-)-and R-(+)-propranolol in transgenic Chinese hamster CHL cell lines expressing CYP3A4, CYP2C18 and CYP2C9.
Enantioselective assay, Propranolol, Transgenic cell, Cytochrome P450, HPLC, Drug metabolism
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曾苏, Qiao Feng Tao, Su Zeng*
J. Biochem. Biophys. Methods 54(2002)103-113,-0001,():
-1年11月30日
Several important chiral phenethylamine agents such as mexiletine, fenfluramine, amphetamine, methamphetamine and N-n-propylamphetamine show stereoselective disposition in humans and large differences in therapeutic relevance and toxicity. To analyze the enantiomers of chiral amine drugs, stereoselective methods were developed to separate those enantiomers on an achiral capillary gas chromatography by pre-column chiral derivatization with S-(-)-N-(fluoroacyl)-prolyl chloride. The stereoselectivity and sensitivity can be improved by chiral derivatization. The methods established offer enantioselective, simple, flexible and economic approaches for the analysis of chiral amine drug enantiomers in biological fluids. The methods have been used to determine S-(+)-methamphetamine in human forensic samples and to analyze enantiomers of amphetamine and fenfluramine in rat liver microsomes.
Chiral derivatization, Gas chromatography, Enantiomers, Chiral amine drug
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曾苏, F.M. Wang a, b, T.W. Yao a, S. Zeng a, *
Journal of Pharmaceutical and Biomedical Analysis 33(2003)317-321,-0001,():
-1年11月30日
A sensitive, simple and accurate method was developed for determination of quercetin and kaempferol in human urine by reversed phase high performance liquid chromatography. The urine samples were analyzed on C18 column. Quercetin and kaempferol were analyzed simultaneously with good separation. UV detector was set at 380nm. There was a linear relationship between chromatographic area of analytes and concentration of analytes over the concentration range 1.638-81.90 and 1.872-93.60ng/ml for quercetin and kaempferol, respectively. The recovery of the assay was 99.79
Flavonoids, High performance liquid chromatography, Disposition, Ginkgo biloba extract
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曾苏, Yi-Hong Tang, Ying He, Tong-wei Yao, Su Zeng*
J. Biochem. Biophys. Methods 59(2004)159-166,-0001,():
-1年11月30日
A stereoselective reversed-phase HPLC assay to determine S-(-) and R-(+) enantiomers of esmolol in human plasma was developed. The method involved liquid–liquid extraction of esmolol from human plasma, using S-(-)-propranolol as the internal standard, and employed 2,3,4,6-tetra-O-acetyl-h-D-glucopyranosyl isothiocyanate as a pre-column chiral derivatization reagent. The derivatized products were separated on a 5-Am reversed-phase C18 column with a mixture of acetonitrile/0.02mol/L phosphate buffer (pH 4.5) (55:45, v/v) as mobile phase. The detection of esmolol derivatives was made at k=224nm with UV detector. The assay was linear from 0.035 to 12Ag/ml for each enantiomer. The analytical method afforded average recoveries of 94.8% and 95.5% for S-(-)-and R-(+)-esmolol, respectively. For each enantiomer, the limit of detection was 0.003Ag/ml and the limit of quantification for the method was 0.035Ag/ml (RSD<14%). The reproducibility of the assay was satisfactory.
Enantiomer separation, Esmolol, RP-HPLC, Diastereoselective chromatography
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曾苏, Lu-Shan Yu, Tong-Wei Yao, Su Zeng*
Chemico-Biological Interactions 146(2003)263-272,-0001,():
-1年11月30日
Zolmitriptan is a novel and highly selective 5-HT1B/1D receptor agonist used as an acute oral treatment for migraine. There are few reports regarding the in vitro metabolism of zolmitriptan. Previous studies indicated zolmitriptan was metabolized via CYP1A2 in human hepatic microsomes. In order to study the enzyme kinetics and drug interaction, the metabolism of zolmitriptan and possible drug–drug interactions were investigated in rat hepatic microsomes induced with different inducers. An active metabolite, N-demethylzolmitriptan, was detected and another minor, inactive metabolite that was reported in human hepatic microsomes was not detected in this study. The enzyme kinetics for the formation of N-demethylzolmitriptan from zolmitriptan in rat liver microsomes pretreated with BNF were 96±22μM (Km), 11±3 pmol min-1 mg protein−1 (Vmax), and 0.12±0.02μl min−1 mg protein−1 (CLint). Fluvoxamine and diphenytriazol inhibited zolmitriptan N-demethylase activity catalyzed by CYP1A2 (Ki=3.8±0.3 and 3.2±0.1μM, respectively). Diazepam and propranolol elicited a slight inhibitory effect on the metabolism of zolmitriptan (Ki=70±11 and 90±18μM, respectively). Cimetidine and moclobemide produced no significant effect on the metabolism of zolmitriptan. Fluvoxamine yielded a kinactivation value of 0.16 min−1, and Ki of 57μM. The results suggest that rat hepatic microsomes are a reasonable model to study the metabolism of zolmitriptan, although there is a difference in the amount of minor, inactive metabolites between human hepatic microsomes and rat liver microsomes. The results of the inhibition experiments provided information for the interactions between zolmitriptan and drugs co-administrated in clinic, and it is helpful to explain the drug-drug interactions of clinical relevance on enzyme level. This study aso demonstrated that fluvoxamine may be a mechanism-based inactivator of CYP1A2.
Zolmitriptan, Microsomes, Cytochrome P450, Metabolism, Interaction
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曾苏, Xiang-Jun Wang, Yi-Hong Tang, Tong-Wei Yao, Su Zeng*
Journal of Chromatography A, 1036(2004)229-232,-0001,():
-1年11月30日
Ion-pairing reversed-phase liquid chromatography (RPLC) was used to separate two polysulfonates, rutin nona(H-) sulfonate sodium and rutin deca(H-) sulfonate sodium, which have very similar chemical structures. The final product always contained both of them when one of the compounds was synthesized. Baseline separation was achieved on a C8-bonded silica column at ambient temperature. The eluent was acetonitrile–15mMphosphate buffer solution containing 20mMTBA(pH 6.0) (46:54, v/v). The calibration plotwas linear in the concentration range 0.5–200μgml−1 for both analytes. The limits of detection (LODs; 254nm) were 0.03μgml−1 for rutin nona(H-) sulfonate sodium and 0.04μgml−1 for rutin deca(H-) sulfonate sodium. Three batches of rutin deca(H-) sulfonate sodium were analyzed using the assay; the results showed that the analytical performance is really satisfactory.
Rutin nona(, H-), sulfonate sodium, Rutin deca(, H-), sulfonate sodium, Flavones,, polysubstituted
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【期刊论文】Cloning and expression of human UDP-glucuronosyltransferase 1A4 in Bac-to-Bac system☆
曾苏, Mingrong Qian, Shuqing Chen, Xin Li, and Su Zeng*
Biochemical and Biophysical Research Communications 319(2004)386-392,-0001,():
-1年11月30日
UDP-glucuronosyltransferases (UGTs) catalyze the transfer of glucuronic acid from uridine diphosphate-glucuronic acid (UDPGA) to compounds with amine, hydroxyl, and carboxylic acid moieties. N-glucuronidation is an important pathway for elimination of many tertiary amine therapeutic agents used in humans. UGT1A4 has been reported to be specific for glucuronidating primary, secondary, and tertiary amines, forming N-glucuronides. To further investigate the drugs metabolized by UGT1A4, the Bac-to-Bac expression system was used to express the recombinant UGT1A4 with His-tag on the C-terminal. The His-tagged recombinant UGT1A4 expressed in Spodoptera frugiperda (Sf9) cells were detected using anti-His antibody and the molecular weight of the recombinant protein was approximately 55kDa. The enzyme activity towards imipramine in cell homogenate protein was found to be 83.14
UDP-glucuronosyltransferase 1A4, Glucuronidation, Bac-to-Bac, HPLC
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曾苏, Yi-Hong Tang, Ying He, Tong-wei Yao, Su Zeng*
Journal of Chromatography B, 805(2004)249-254,-0001,():
-1年11月30日
A stereoselective RP-high performance liquid chromatography (HPLC) assay to determine simultaneously the enantiomers of esmolol and its acid metabolite in human plasma was developed. The method involved a solid-phase extraction and a reversed-phase chromatographic separation with UV detection (λ=224nm) after chiral derivatization. 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl isothiocyanate (GITC) was employed as a pre-column chiral derivatization reagent. The assay was linear from 0.09 to 8.0μg/ml for each enantiomer of esmolol and 0.07-8.0μg/ml for each enantiomer of the acid metabolite. The absolute recoveries for all enantiomers were>73%. The intra-and inter-day variations were<15%. The validated method was applied to quantify the enantiomers of esmolol and its metabolite in human plasma for hydrolysis studies.
Enantiomer separation, Esmolol
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