Full-Text Search:
Home|Journal Papers|About CNKI|User Service|FAQ|Contact Us|中文
《Computers and Applied Chemistry》 2011-02
Add to Favorite Get Latest Update

Theoretical study on the degradation mechanism of lamivudine

Wang Xuejie and You Jinzong (School of Science and Technology,Zhejiang International Studies University,Hangzhou,310012,Zhejiang,China)  
Lamivudine(LMVD) is an important inhibitor for HIV.For a better understanding the degradation mechanism of LMVD and validating the experiments of Bedse G et al.Based on the quantum chemical software named GAMESS,we studied the electronic structures of LMVD and intermediates during the hydrolysis,oxidation,and MS~n processes.Using the Hartree-Fock method at the level 3-21G,the conformations,atomic net charges,bond orders,dipole moments and potential energies of these compounds in the neutral,acidic,alkaline and oxidative conditions were obtained.Then,the degradation mechanisms of LMVD under the various conditions and the fragmentation mechanisms of MS" were derived.The results indicated that LMVD remained stable in neutral,while it showed instability in acidic and alkali solutions.The degradation pathways of LMVD were similar in acidic and alkali solutions.There were two kind hydrolytic mechanisms.One pathway was that the nucleophilic reaction occurred at C6 site,the C6-N7 bond to be cleaved,and the degradation productⅤto be brought,then the second nucleophilic reaction occurred at C8 site,the N3-C8 bond to be cleaved,and the productⅡto be brought;other pathway was that the nucleophilic reaction occurred at C8 site,the N3-C8 bond to be cleaved,and the degradation productⅠto be brought.In alkali condition,the hydroxyl group had stronger nucleophilicity,the atomic net charges and bond orders were favorable to the nucleophilic reaction,so that,the rate of hydrolysis was faster than in acidic condition.In the H_2O_2 solution, LMVD could be oxidated,but the oxidative productsⅢandⅣwere difficult to be hydrolyzed due to their more stable than LMVD.The bond cleavage of MS occurred primarily at the weakest bonds.The outcomes of our investigation were highly consistent with the results of Bedse G et al.It indicated that it was easy and convenient to presume and explain the degradation mechanism and MS pathways of drugs by using of GAMESS quantum chemical software.
【Key Words】: lamivudine(LMVD) quantum chemistry hydrolysis mechanism
【Fund】: 浙江省重点科研项目(2006C21092)
【CateGory Index】: R91
Download(CAJ format) Download(PDF format)
CAJViewer7.0 supports all the CNKI file formats; AdobeReader only supports the PDF format.
Chinese Journal Full-text Database 3 Hits
1 TIAN Chun-lian,XIAO Zhuo-bing(Key Laboratory for Forest Products and Chemical Industry Engineering,Jishou University,Zhangjiajie 427000,China);Thermal Decomposition Mechanism and Kinetics of Lycorine Hydrochloride[J];Chemistry and Industry of Forest Products;2012-05
2 XIAO Zhuo-bing XIAO Zhuo-bing,GUO Man-man,GUO Rui-ke,TIAN Chun-lian(Key Laboratory for Forest Products and Chemical Industry Engineering,Jishou University,Zhangjiajie 427000,China);Purity,Thermal Decomposition Kinetics and Shelflifeof Artemisinin by Thermal Analysis[J];Chemistry and Industry of Forest Products;2013-01
3 ZHAN Xue-yan;ZHANG Yan-ling;ZHANG Jia-yu;TAN Peng;JI Jiao-jiao;DONG Jie;LIU Yong-gang;Beijing University of Chinese Medicine;;Fragmentation Pathways and Patterns of Asiaticoside and Madecassoside in ESI-MS~n[J];Journal of Chinese Mass Spectrometry Society;2015-04
Chinese Journal Full-text Database 3 Hits
1 ZHANG Zhao-ying( Xuzhou clinical pharmacology research centre of Jiangsu province, Xuzhou Jiangsu 221005 , China);Clinical research progress on Lamivudine[J];Anti-infection Phurmacy;2005-01
2 SHAO Li - hua, MA Li - xian, SUN Shu - ai, PAN Yu - zhen and WANG Xin - ting (Department of Health Chemistry, School of Public Health, Shandong University, Jinan 250012);Determination of Lamivudine Concentration in Human Serum by HPLC[J];Chinese Journal of Pharmaceutical Analysis;2002-01
3 LI Meng,LIU You-ping,LU Jing,DI Xin(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China);RP-HPLC determination of lamivudine and its related substances[J];Chinese Journal of Pharmaceutical Analysis;2009-07
Chinese Journal Full-text Database 10 Hits
1 CHAI Yi-feng, WU Yu-tian and LI Xiang(Department of Pharmaceutical Analysis, College of Pharmacy, Second Military Medical University, Guohe Road 325, Shanghai 200433), Fenxi Shiyanshi,2004,23(6):71~92;Pharmaceutical Analysis I[J];Analytical Laboratory;2004-06
3 LIU Wei-wei,GONG Feng,CHENG Liang,ZHAO Yue-qiang,TANG Li-juan(School of Chemical Engineering,Huaihai Institute of Technology,Lianyungang 222005,China);Advancement in the Synthesis and Application of Lamivudine[J];Journal of Huaihai Institute of Technology(Natural Sciences Edition);2008-03
4 LI Yong1,WANG Zhi-ling1,HAO Er-jun2(1.Department of Chemistry,Henan Institute of Education,Zhengzhou 450046,China;2.College of Chemistry and Environmental Sciences,Henan Normal University,Xinxiang 453007,China);Determination of Residual Organic Solvents in Lamivudine by Headspace Gas Chromatography[J];Journal of Henan Institute of Education(Natural Science Edition);2010-04
5 GUO Hua1,CHENG Shi-de2(1.School of Medicine,Ezhou University,2.Erzhou Hospital of TCM,Ezhou 436000,China);Therapeutic observation of combination of adefovir and lamivudine in HBeAg-negative adults with chronic hepatitis B virus infection and clinical resistance to lamivudine[J];Chinese Journal of Biochemical Pharmaceutics;2010-06
6 QU Liang~1,SUN Lu~(1*),LIU Jie~2 (1.School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China;2.North East Pharmaceutical Group Marketing Co.,Ltd.,Shenyang 110023,China);Identification of the related substances in lamivudine by LC-MS[J];Journal of Shenyang Pharmaceutical University;2013-04
7 DONG Fang;Zibo Food and Drug Inspection & Testing Center;;Determination of Lamivudine Tablets by HPLC[J];Food and Drug;2015-03
8 YANG Zheng1,3,LIAO Chang-jun2,ZHONG Yuan-gao2,et al(1.Department of Experimental Technology,Chengdu Medical College,Chengdu 610083;2.Department of Pharmacy,Chengdu Medical College,Chengdu 610083;3.West China Medical Centre,Sichuan University,Chengdu 610041,China);Determination of lamivudine in urine with RP-HPLC[J];Medical Journal of West China;2009-07
9 LI Zhong-kun1,LI Hui-qing2,LIU Yan-qiu1,ZHAO Ai-ming2,REN Xiao-ming (1.Department of Pharmacy,Yanan Hospital of Kunming,Yunnan Kunming 650051,China;2 Yunnan AIDS Care Center,Yunan Kunming 650301,China);The method of determination of methadone hydrochloride in plasma by HPLC in patients of anti-virus treatment[J];Chinese Journal of Hospital Pharmacy;2008-17
10 WANG Yang, LIU Wen-tao ,ZHANG Hong, BI Kai-shun, CHEN Xiao-hui (Department of Medical Analysis , Shenyang Pharmaceutical University, Liaoning Shenyang 110016, China);Determination of lamivudine in human plasma by LC-MS[J];Chinese Journal of Hospital Pharmacy;2010-19
Chinese Journal Full-text Database 10 Hits
1 HUANG Yun-Hong1, ZHANG Sheng-Hua1, ZHEN Rui-Xian2, XU Xian-Dong1, ZHEN Yong-Su1 1.Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing,100050, P.R.China 2.The First Peoples Hospital of Kaiping City, Kaiping,Guangdong,529300, P.R.China;Asiaticoside Inducing Apoptosis of Tumor Cells and Enhancing Anti-tumor Activity of Vincristine[J];Chinese Journal of Cancer;2004-12
2 Sun Weixing, Liu Zhiqiang, Liu Shuying (Changchun Institute of Applied Chemisty,Chinese Academy of Sciences, Changchun 130022 );Application of Electrospray Mass Spectrometry for Study of Specific Noncovalent Large Biomolecule -organic Molecule Complexes in Solution[J];Chinese Journal of Analytieal Chemistry;1998-01
3 ZHU Xiao-mei(School of Chemistry,Shaanxi University of Technology,Shaanxi Hanzhong 723001,China);Thermal Stability and Thermal Decomposition Kinetics of Ofloxacin[J];Chemical World;2008-06
4 Wang,Shaoxua Tan,Zhicheng,b Che,Ruxina Li,Yanshenga(a College of Environmental Science & Engineering,Dalian Jiaotong University,Dalian 116028)(b China Ionic Liquid Laboratory and Thermochemistry Laboratory,Dalian Institute of Chemical Physics,Chinese Academy of Sciences,Dalian 116023);Thermal Stability and Kinetics of Thermal Decomposition of Salvianolic Acid B[J];Acta Chimica Sinica;2012-02
5 HUANG Baoxiang1,FU Shugen1,ZHU Peilin1,DENG Xiaomei2(1.Jiangxi Academy of Forestry,Nanchang Jiangxi 330013,China; 2.College of Forestry,South China Agricultural University,Guangzhou Guangdong 510000,China);Study on the Lycorin of Lycoris Plants[J];Jiangxi Forestry Science and Technology;2012-01
6 ZHENG Zhi-feng1,HUANG Yuan-bo1,JIANG Jian-chun2,YANG Xiao-qin1,ZHOU Ling1(1.Key Laboratory of Forest Resources Conservation and Use in the Southwest Mountains of China(SWFU),Ministry of Education;Faculty of Wood Science and Technology,Southwest Forestry University,Kunming 650224,China;2.Institute of ChemicalIndustry of Forest Products,CAF;National Engineering Lab.for Biomass Chemical Utilization;Key and Open Lab.onForest Chemical Engineering,SFA;Key Lab.of Biomass Energy and Material,Jiangsu Province,Nanjing 210042,China);Study on Pyrolysis Characteristics and Kinetics of Walnut Shell[J];Chemistry and Industry of Forest Products;2010-02
7 HUANG Yuan-bo1,ZHENG Zhi-feng1,JIANG Jian-chun2,DAI Wei-di2,SUN Yun-juan2(1.Key Laboratory of Forest Resources Conservation and Use in the Southwest Mountains of China(SWFU),Ministry of Education;College of Material Engineering,Southwest Forestry University,Kunming 650224,China; 2.Institute of Chemical Industry of Forest Products,CAF;National Engineering Laboratory for Chemical Utilization of Biomass;Key and Open Lab.of Forest Chemical Engineering,SFA;Key Lab.of Biomass Energy and Material,Jiangsu Province,Nanjing 210042,China);Thermogravimetric Analysis and Kinetics of Walnut Shell and Coal Co-pyrolysis[J];Chemistry and Industry of Forest Products;2012-02
8 Zhang Zhuo,et al Department of Pharmacology,Luzhou Medical College;Aisaticoside amelioratses the memory capacity on rat of Alzheimer’s disease model[J];Journal of Luzhou Medical College;2012-06
9 Tan Peng,Guan Jun,Liu Yonggang,Li Fei,Qiao Yanjiang(School of Chinese Pharmacy,Beijing University of Chinese Medicine,Beijing 100102,China);Quantum Chemistry Calculation on Demethylated Metabolites of Aconitine[J];World Science and Technology(Modernization of Traditional Chinese Medicine and Materia Medica);2011-05
10 CUI Pei-shen,ZHANG Nai-feng,WANG Meng,ZHANG Shu-ting,REN Heng-xin, SUN Chang-hai,FANG Hong-zhuang(Pharmaceutical College of Jiamusi University,Jiamusi 154007,China);Study on Mass Behavior and Fragment Ions of Rhein by ESI-IT MS and Quantum Chemistry[J];Journal of Instrumental Analysis;2013-04
【Secondary Citations】
Chinese Journal Full-text Database 5 Hits
1 CHEN Yaxi, GUO Shuhua, QI Zhenyuan, et al. Institute for Viral Hepatitis, Chongqing University of Medical Sciences, Chongqing 400010, China;Experimental study on the effect of combination therapy with lamivudine and famciclovir against duck hepatitis B virus in vivo[J];Chinese Journal of Hepatology;2001-04
2 YUAN Guiyu, DUAN Yili, WANG Fengshui, LIANG Shuren and ZHU Limin. Tianjin Infectious Disease Hospital, Tianjin 300192, China;Prevention and treatment of HBV reinfection following liver transplantation[J];Chinese Journal of Hepatology;2002-01
3 ZHENG Shusen,WU Jian,WANG Weilin,HUANG Dongsheng, LIANG Tingbo, LU Anwei. Department of Hepatobiliary Surgery,The First Affiliated Hospital of Medical College of Zhejiang University,Hangzhou 310003, China;Lamivudine as prophylaxis against hepatitis B virus reinfection following orthotopic liver transplantation[J];National Medical Journal of China;2002-07
4 YAO Guangbi, WANG Bao'en, CUI Zhenyu, et al. Shanghai Jing An Qu Central Hospital, Shanghai 200040;Two years trial of lamivudine for the treatemnt of chronic hepatitis B[J];CHINESE HEPATOLOGY;2000-03
5 LIU Li ping,ZHANG Ling xia( Pharmacy Department,302 Hospital of PLA,Beijing 100039,China);Lamivudine for hepatitis B:antiviral efficacy and viral resistance[J];Chinese New Drugs Journal;2003-06
©2006 Tsinghua Tongfang Knowledge Network Technology Co., Ltd.(Beijing)(TTKN) All rights reserved