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Screening of new non-nucleoside reverse transcriptase inhibitors of HIV-1 based on traditional Chinese medicines database
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作者 Tao Liu Ai Xiu Li +2 位作者 YOU Pan Miao Ke Zhu Wu Yi Ma 《Chinese Chemical Letters》 SCIE CAS CSCD 2009年第11期1386-1388,共3页
HIV- 1 RT is an important target for the treatment of AIDS. There are two major classes of antiviral agents that inhibit HIV- 1 RT have been identified, nucleoside RT inhibitors (NRTIs) and non-nucleoside RT inhibit... HIV- 1 RT is an important target for the treatment of AIDS. There are two major classes of antiviral agents that inhibit HIV- 1 RT have been identified, nucleoside RT inhibitors (NRTIs) and non-nucleoside RT inhibitors (NNRTIs). In this report, a noval class of non-nucleoside compound with potential RT inhibitory activity were found from the traditional Chinese medicines database (TCMD) using a combination of virtual screening, docking, molecular dynamic simulations, where results were ranked by scoring function of the docking tool. The result indicates that M4753 (a compound derived from TCMD) has not only the lowest bonding energy but also the best match in geometric conformation with the forthcoming NNRTIs. Accordingly M4753 might possibly become a promising lead compound of NNRTIs for AIDS therapy. 展开更多
关键词 non-nucleoside reverse transcriptase inhibitors (NNRTIs) Traditional Chinese medicines database (TCMD) Virtual screening Molecular dock Molecular dynamic simulation
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Synthesis and biological evaluation of novel 1-aryl-5-iodo-6-benzyluracils as potent HIV-1 non-nucleoside reverse transcriptase inhibitors
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作者 王惟 李立 +5 位作者 刘畅 张亮 闫寒 张志丽 王孝伟 刘俊义 《Journal of Chinese Pharmaceutical Sciences》 CAS 2010年第4期312-317,共6页
We have synthesized the novel compounds 1a-1i,which are a series of hybrid analogues to 6-benzyl-1-(benzyloxymethyl)- 5-iodouracil,a compound showing strong activity against HIV-1.We also evaluated the activity of t... We have synthesized the novel compounds 1a-1i,which are a series of hybrid analogues to 6-benzyl-1-(benzyloxymethyl)- 5-iodouracil,a compound showing strong activity against HIV-1.We also evaluated the activity of these compounds as the inhibitors of HIV-1 reverse transcriptase(HIV-1 RT),and they have demonstrated moderate activity. 展开更多
关键词 HIV-1 reverse transcriptase non-nucleoside reverse transcriptase inhibitors l-[(2-Hydroxyethoxy)methyl]-6-phenylthiothymine
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Molecular Modeling of Quinoline-Based Compounds as Potential Dual Inhibitors of Reverse Transcriptase and Integrase of HIV 被引量:1
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作者 Alberto Cabrera Leonor Huerta Hernández +1 位作者 Daniel Chávez José L. Medina-Franco 《Computational Molecular Bioscience》 2018年第3期122-148,共27页
As follow-up of our past publication?[1], we propose that quinolones (as part of the pyridinone family) are capable to increase the number of interactions with HIV reverse transcriptase (RT) or integrase (IN) by addin... As follow-up of our past publication?[1], we propose that quinolones (as part of the pyridinone family) are capable to increase the number of interactions with HIV reverse transcriptase (RT) or integrase (IN) by adding a halogen in position C-8 of aromatic portion of the quinolones. This addition could help with the activity of dual inhibitors of RT and IN. In this work, we add a chlorine atom with the rationale to identify in the docking simulations a halogen interaction with the oxygen in the near aminoacids in the binding pockets of RT and IN enzymes. Our docking studies started with RT and 320 structures. Later, we took 73 structures with good results in docking with RT. The structures that we choose contain ester or acids groups in C-3 due the structural similarity with groups in charge to interact with the Mg++ ions in Elvitegravir. In conclusion, we obtained 14 structures that could occupy the allosteric pocket of RT and could inhibit the catalytic activity of IN, for this reason could be dual inhibitors. A major perspective of this work is the synthesis and testing of the potential dual inhibitors designed. 展开更多
关键词 reverse transcriptase INTEGRASE QUINOLONE Dual inhibitor DOCKING
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The Effects of Reverse Transcriptase Inhibitor on Radiosensitization of Human Malignant Glioma Cells
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作者 Jing DAI Fu-Xiang ZHOU Cong-Hua XIE Zhi-Guo LUO Yun-Feng ZHOU~Δ(Department of Radio-Chematherapy of Zhongnan Hospital and Cancer Research Center, Wuhan University, Wuhan 430071, China) 《生物医学工程学杂志》 EI CAS CSCD 北大核心 2005年第S1期121-122,共2页
关键词 The Effects of reverse transcriptase inhibitor on Radiosensitization of Human Malignant Glioma Cells DSB AZT
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Synthesis and anti-HIV-1 activity evaluation of N-1-alkyl-5-halogeno-6-alkylamino uracils as novel non-nucleoside HIV-1 reverse transcriptase inhibitors
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作者 闫寒 王孝伟 +2 位作者 郭盈 张志丽 刘俊义 《Journal of Chinese Pharmaceutical Sciences》 CAS 2011年第2X期146-153,共8页
N-1-alkyl-5-halogeno-6-alkylamino uracils,which are novel 1-[(2-hydroxyethoxy) methyl]-6-(phenylthio) thymine (HEPT) analogues,were synthesized as the selective and potent non-nucleoside human immunodeficiency virus(H... N-1-alkyl-5-halogeno-6-alkylamino uracils,which are novel 1-[(2-hydroxyethoxy) methyl]-6-(phenylthio) thymine (HEPT) analogues,were synthesized as the selective and potent non-nucleoside human immunodeficiency virus(HIV)-1 reverse transcriptase inhibitors.Some of the compounds showed potent inhibitory activity against HIV-1 reverse transcriptase.For instance,compounds 1d,1m and 1n exhibited potent anti-HTV-1 activity with the IC_(50) values of 13.3,11.7 and 3.15μM,respectively, which are comparable to that of nevirapine(IC_(50) 8.38μM). 展开更多
关键词 HIV-1 reverse transcriptase non-nucleoside reverse transcriptase inhibitors HEPT analogues
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Synthesis and biological evaluation of novel 2-arylalkylthio-5-iodo-6-benzyl S-DABOs as potent non-nucleoside HIV-1 reverse transcriptase inhibitors 被引量:1
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作者 Liang Zhang Xiao-Wei Wang Jun-Yi Liu 《Journal of Chinese Pharmaceutical Sciences》 CAS 2012年第1期28-32,共5页
A series of novel dihydro-alkylthio-benzyl-oxopyrimidines (S-DABOs) 7a-f have been designed and synthesized with an efficient method. Biological evaluation of their HIV-1 reverse transcriptase inhibitory activities ... A series of novel dihydro-alkylthio-benzyl-oxopyrimidines (S-DABOs) 7a-f have been designed and synthesized with an efficient method. Biological evaluation of their HIV-1 reverse transcriptase inhibitory activities was performed using Nevirapine (NVP) as a reference compound. Among the series, compound 7d shows the highest reverse transcriptase inhibitory activity, which is better than Nevirapine. 展开更多
关键词 HIV-1 RT non-nucleoside reverse transcriptase inhibitors S-DABOs
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Synthesis and anti-HIV-1 activity evaluation of N-l-alkyl-5-halogeno-6- alkylamino uracils as novel non-nucleoside HIV-I reverse transcriptase inhibitors
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作者 Han Yan Xiao-Wei Wang +2 位作者 Ying Guo Zhi-Li Zhang Jun-Yi Liu 《Journal of Chinese Pharmaceutical Sciences》 CAS 2011年第2期146-153,共8页
N-l-alkyl-5-halogeno-6-alkylamino uracils, which are novel l-[(2-hydroxyethoxy) methyl]-6-(phenylthio) thymine (HEPT) analogues, were synthesized as the selective and potent non-nucleoside human immunodeficiency... N-l-alkyl-5-halogeno-6-alkylamino uracils, which are novel l-[(2-hydroxyethoxy) methyl]-6-(phenylthio) thymine (HEPT) analogues, were synthesized as the selective and potent non-nucleoside human immunodeficiency virus (HIV)-I reverse transcriptase inhibitors. Some of the compounds showed potent inhibitory activity against HIV-1 reverse transcriptase. For instance, compounds ld, lm and In exhibited potent anti-HIV-1 activity with the ICso values of 13.3, 11.7 and 3.15 μM, respectively, which are comparable to that of nevirapine (IC50 8.38 μM). 展开更多
关键词 HIV-1 reverse transeriptase non-nucleoside reverse transcriptase inhibitors HEPT analogues
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Liver injury in HIV-1-infected patients receiving non-nucleosides reverse transcriptase inhibitors-based antiretroviral therapy 被引量:1
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作者 LI Zai-cun LI Hong-jun +6 位作者 DAI Li-li GAO Yan-qing CAI Wei-ping LI Hai-ying HUANG Xiao-jie ZHANG Tong WU Hao 《Chinese Medical Journal》 SCIE CAS CSCD 2010年第24期3587-3590,共4页
Background Liver injury is one of the most important adverse effects of antiretroviral therapy, leading to therapy changing or discontinuation. Data on liver injury in human immunodeficiency virus-1-infected patients ... Background Liver injury is one of the most important adverse effects of antiretroviral therapy, leading to therapy changing or discontinuation. Data on liver injury in human immunodeficiency virus-1-infected patients receiving antiretroviral therapy are limited in China. The purpose of this study was to investigate the features of liver injury in human immunodeficiency virus type 1-infected patients receiving non-nucleosides reverse transcriptase inhibitors-based antiretroviral therapy in China.Methods Seventy-five patients on antiretroviral therapy containing non-nucleosides reverse transcriptase inhibitors were retrospectively studied. The patients were divided into 2 groups: group 1 (with liver injury, n=45) and group 2(without liver injury, n=30). The features of liver injury were analyzed. The sex, age, baseline CD4 counts, hepatitis B virus (HBV) and/or hepatitis C virus (HCV) co-infection, hepatotoxic drug use and nevirapine or efavirenz use were compared between two groups.Results Forty-five patients (60.0%), 31 (68.9%) males and 14 (31.1%) females, aged 12 to 52 years (averaged (3g±9)years), experienced at least one episode of liver injury. Forty (53.3%) patients were co-infected with HBV and/or HCV, 42 (56%) patients had concomitant use of antituberculosis drugs or cotrimoxazole, 46 (61.3%) and 29 (38.7%) patients received regimen containing nevirapine and efavirenz, respectively. Grade 1 liver injuries were observed in 26 (57.8%)patients, grade 2 in 16 (35.6%), grade 3 in 2 (4.0%) and grade 4 in 1 (2.2%). Three (6.7%) patients discontinued highly active antiretroviral therapy (HAART) due to liver injury. In group 1, there were 29 (64.4%) patients co-infected with HBV and/or HCV, 32 (71.1%) patients received regimen containing nevirapine, and 30 (66.7%) patients had concomitant use of anti-tuberculosis drugs or cotrimoxazole, respectively, significantly higher than those in group 2 (11 (36.7%), 14 (46.7%)and 12 (40%), respectively; P=0.018, 0.033, 0.023, respectively). The sex, age, baseline CD4 counts and disease stage were not factors associated with liver injury.Conclusions Liver injury associated with HAART containing non-nucleosides reverse transcriptase inhibitors was mild to moderate and those who were co-infected with HBV and/or HCV, had concomitant use of antituberculosis drugs or cotrimoxazole and received a regimen containing nevirapine were prone to liver injury while receiving HAART. 展开更多
关键词 human immunodeficiency virus liver injury non-nucleosides reverse transcriptase inhibitor antiretroviral therapy
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2019—2022年北京某院HIV-1新发感染者抗病毒治疗前耐药情况分析 被引量:1
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作者 李莉 安希钊 +1 位作者 粟斌 刘利锋 《现代医药卫生》 2024年第12期1990-1995,共6页
目的 了解2019—2022年该院新发1型人类免疫缺陷病毒(HIV-1)感染者中原发耐药水平和流行现状。方法 对2019—2022年HIV-1确认阳性且未行抗病毒治疗的新发感染者进行原发耐药检测。应用反转录/巢式聚合酶链式反应扩增病毒pol基因,进行病... 目的 了解2019—2022年该院新发1型人类免疫缺陷病毒(HIV-1)感染者中原发耐药水平和流行现状。方法 对2019—2022年HIV-1确认阳性且未行抗病毒治疗的新发感染者进行原发耐药检测。应用反转录/巢式聚合酶链式反应扩增病毒pol基因,进行病毒亚型、主要耐药相关突变和原发耐药率分析等。结果 2019—2022年新发HIV-1感染者进行原发耐药检测比例分别为62.23%(669/1 075)、80.00%(400/500)、 80.78%(500/619)及81.03%(474/585),原始耐药发生比例分别为5.31%(30/565)、6.65%(24/361)、6.59%(30/455)及4.19%(18/430),总耐药比例为5.63%(102/1 811)。蛋白酶抑制剂、核苷类反转录酶抑制剂(NRTIs)、非核苷类反转录酶抑制剂(NNRTIs)耐药率分别为0.11%(2/1 811)、1.44%(26/1 811)、4.91%(89/1 811);NNRTIs类耐药位点主要是V179D/E单独或与其他位点协同出现;NRTIs类耐药位点主要是M184V及K65R。主要感染亚型依次为CRF01_AE[44.56%(807/1 811)]、CRF07_BC[39.54%(716/1 811)]、B亚型[8.28%(150/1 811)]。结论 该院新诊断HIV-1感染者进行原发耐药检测比例逐年上升,近3年来原发耐药率呈下降趋势,原发耐药呈低流行水平,主要原发耐药为NNRTIs及NRTIs耐药。 展开更多
关键词 艾滋病病毒 新发感染 亚型 原发耐药 核苷类反转录酶抑制剂 非核苷类反转录酶抑制剂
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接受不同抗逆转录病毒治疗方案的HIV感染者血浆中可溶性炎症标志物水平差异研究
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作者 李义福 苏乙花 苏民 《中国性科学》 2024年第3期131-135,共5页
目的探究接受不同抗逆转录病毒治疗(ART)方案的人类免疫缺陷病毒(HIV)感染者血浆中可溶性炎症标志物表达水平的差异。方法选取2019年6月至2021年6月于海南省中医院就诊的初诊HIV感染者100例,随机将患者分为非核苷类逆转录酶抑制剂(NNRTI... 目的探究接受不同抗逆转录病毒治疗(ART)方案的人类免疫缺陷病毒(HIV)感染者血浆中可溶性炎症标志物表达水平的差异。方法选取2019年6月至2021年6月于海南省中医院就诊的初诊HIV感染者100例,随机将患者分为非核苷类逆转录酶抑制剂(NNRTI)组和整合酶链转移抑制剂(INSTI)组,各50例。所有患者基础用药为恩曲他滨替诺福韦片,NNRTI组患者联用依非韦伦片,INSTI组患者联用拉替拉韦钾片。分别于治疗前及治疗6个月后随访,比较两组患者血生化指标、T细胞计数、病毒学指标、炎性细胞因子表达。结果治疗6个月后两组患者血生化指标、T细胞计数、病毒学指标及血浆炎性细胞因子表达水平较治疗前均有显著差异(P<0.05),且INSTI组患者各项指标改变更显著(P<0.05)。结论相比NNRTI,应用INSTI更有助于降低HIV感染者全身炎症水平,且药物抑制病毒效果显著。 展开更多
关键词 人类免疫缺陷病毒 抗逆转录病毒治疗 非核苷类逆转录酶抑制剂 整合酶链转移抑制剂 炎性细胞因子
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HIV非核苷酸逆转录酶抑制剂的合成
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作者 王奕程 《山西化工》 CAS 2024年第1期37-41,共5页
获得性免疫缺陷综合症作为一种无声、致命的杀手,是当今世界最为严重的传染性疾病之一。逆转录酶是HIV病毒增殖所需的重要蛋白质,目前非核苷酸逆转录酶抑制剂以其较高的特异性而被广泛采用。本文将关注于三种经典的HIV非核苷酸逆转录酶... 获得性免疫缺陷综合症作为一种无声、致命的杀手,是当今世界最为严重的传染性疾病之一。逆转录酶是HIV病毒增殖所需的重要蛋白质,目前非核苷酸逆转录酶抑制剂以其较高的特异性而被广泛采用。本文将关注于三种经典的HIV非核苷酸逆转录酶抑制剂Rilpivirine、Etravirine以及Doravirine的化学合成,从最初产率较低、耗时较长的合成出发,通过采用微波辐射、正交实验以及有机金属催化反应达到合成最优化的目的。最优化的过程不仅仅局限于对反应路线的改进,还有在反应路线的基础上小尺度地对反应参数的最优化。 展开更多
关键词 有机合成 有机合成最优化 获得性免疫缺陷综合症 非核苷酸逆转录酶抑制剂
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Interleukin-1 beta up-regulates tissue inhibitor of matrix metalloproteinase-1 mRNA and phosphorylation of c-jun N-terminal kinase and p38 in hepatic stellate cells 被引量:22
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作者 Ya-Ping Zhang Xi-Xian Yao Xia Zhao 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第9期1392-1396,共5页
AIM: To study the relationship between interleukin-lbeta (IL-1β) up-regulating tissue inhibitor of matrix metalloproteinase-1 (TIMMP-1) mRNA expression and phosphorylation of both c-jun N-terminal kinase (INK)... AIM: To study the relationship between interleukin-lbeta (IL-1β) up-regulating tissue inhibitor of matrix metalloproteinase-1 (TIMMP-1) mRNA expression and phosphorylation of both c-jun N-terminal kinase (INK) and p38 in rat heffatic stellate cells (HSC). METHODS: RT-PCR was performed to measure the expression of TIMMP-1 mRNA in rat HSC. Western blot was performed to measure IL-1β-induced JNK and p38 activities in rat HSC. RESULTS: TIMMP-1 mRNA expression (1.191± 0.079) was much higher after treatment with IL-1β (10 ng/mL) for 24 h than in control group (0.545±0.091) (P〈0.01). IL-1β activated INK and p38 in a time-dependent manner. After stimulation with IL-1β for 0, 5, 15, 30, 60 and 120 min, the INK activity was 0.982±0.299, 1.501±0.720, 2.133±0.882, 3.360±0.452, 2.181±0.789, and 1.385 ± 0.368, respectively. There was a significant difference in JNK activity at 15 min (P〈 0.01), 30 min (P〈 0.01) and 60 min (P〈0.01) in comparison to that at 0 min. The p38 activity was 1.061±0.310, 2.050±0.863, 2.380±0.573, 2.973±0.953, 2.421±0.793, and 1.755 ± 0.433 at the 6 time points (0, 5, 15, 30, 60 and 120 min) respectively. There was a significant difference in p38 activity at 5 min (P〈0.05), 15 min (P〈0.01), 30 min (P〈0.01) and 60 min (P〈0.01) compared to that at 0 min. TIMMP-1 mRNA expression trended to decrease in 3 groups pretreated with different concentrations of SP600125 (10 μmol/L, 1.022±0.113; 20 μmol/L, 0.869±0.070; 40 μmol/L, 0.666±0.123). Their decreases were all significant (P〈0.05, P〈0.01, P〈0.01) in comparison to control group (without SP600125 treatment, 1.163±0.107). In the other 3 groups pretreated with different concentrations of SB203580 (10 μmol/L, 1.507±0.099; 20 μmol/L, 1.698±0.107; 40 μmol/L, 1.857±0.054), the expression of TIMMP-1 mRNA increased. Their levels were higher than those in the control group (without SB203580 treatment, 1.027 ± 0.061) with a significant statistical significance (P〈 0.01). CONCLUSION: IL-1β has a direct action on hepatic fibrosis by up-regulating TIMMP-1 mRNA expression in ratessionin in rate HSC.JNK and p38 mitogen-activated protein kinases (MAPKs) are involved in IL-1β-induced TIMMP-1 gene expression, and play a distinct role in this process, indicating that p38 and .INK pathways cooperatively mediate TIMP-1 mRNA expression in rat HSC. 展开更多
关键词 Up-Regulation Animals ANTHRACENES Blotting Western Cell Line Enzyme inhibitors IMIDAZOLES INTERLEUKIN-1 JNK Mitogen-Activated Protein Kinases Liver Liver Cirrhosis PHOSPHORYLATION PYRIDINES RNA Messenger Rats reverse transcriptase Polymerase Chain Reaction Signal Transduction Time Factors Tissue inhibitor of Metalloproteinase-1 p38 Mitogen-Activated Protein Kinases
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依非韦伦致男性乳房发育1例分析
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作者 唐炯 刘颖 《中国药物警戒》 2023年第11期1306-1308,共3页
目的 探讨非核苷类反转录酶抑制剂依非韦伦致男性乳房发育病例,为临床预防及处理其不良反应提供参考。方法 分析1例感染人类免疫缺陷病毒(HIV)男性患者服用依非韦伦导致乳房发育的治疗过程,探讨依非韦伦致乳腺增生的机理并排除其他药物... 目的 探讨非核苷类反转录酶抑制剂依非韦伦致男性乳房发育病例,为临床预防及处理其不良反应提供参考。方法 分析1例感染人类免疫缺陷病毒(HIV)男性患者服用依非韦伦导致乳房发育的治疗过程,探讨依非韦伦致乳腺增生的机理并排除其他药物的可能性。结果 患者服用依非韦伦后单侧乳房发育,停用该药并予以手术治疗2个月后,乳房不适减轻。结论 依非韦伦致男性乳房发育或与影响雌激素/雄激素的作用有关,用药期间应定期做乳房检查,做到早识别、早处理。 展开更多
关键词 依非韦伦 男性乳房发育 人类免疫缺陷病毒 获得性免疫缺陷综合征 药品不良反应 抗逆转录病毒治疗 非核苷逆转录酶抑制剂
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奈韦拉平的合成 被引量:12
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作者 孟庆伟 曾伟 +2 位作者 赖琼 李悦青 赵伟杰 《中国医药工业杂志》 CAS CSCD 北大核心 2006年第1期5-7,共3页
氰乙酰胺和乙酰乙酸乙酯经缩合环合、氯化、氰基水解、霍夫曼降解、催化氢解脱氯、选择性氯化制得2-氯-3-氨基-4-甲基吡啶,再与2-氯烟酰氯进行酰胺化反应、环丙胺亲核取代和闭环反应生成奈韦拉平,总产率39%。
关键词 奈韦拉平 逆转录酶抑制剂 抗病毒药 合成
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富马酸泰诺福韦酯新合成路线 被引量:12
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作者 武卫 唐磊 +2 位作者 邓银来 顾维 张荣久 《中国药科大学学报》 CAS CSCD 北大核心 2010年第6期505-507,共3页
对富马酸泰诺福韦酯的新合成路线进行研究。以R-环氧氯丙烷为起始原料,通过常压氢化制得R-1-氯-2-丙醇(7),化合物7与多聚甲醛和氯化氢气体反应得R-1-氯-2-氯甲基丙烷(6),化合物6与亚磷酸三乙酯反应得R-(2-甲基-1-氯乙基)氧甲基膦酸二乙... 对富马酸泰诺福韦酯的新合成路线进行研究。以R-环氧氯丙烷为起始原料,通过常压氢化制得R-1-氯-2-丙醇(7),化合物7与多聚甲醛和氯化氢气体反应得R-1-氯-2-氯甲基丙烷(6),化合物6与亚磷酸三乙酯反应得R-(2-甲基-1-氯乙基)氧甲基膦酸二乙酯(5),化合物5与腺嘌呤缩合后再经脱酯反应得到关键中间体R-9-(2-膦酸甲氧基丙基)-腺嘌呤(3,泰诺福韦)。化合物3经酯化、成盐得到最终产物富马酸泰诺福韦酯。合成富马酸泰诺福韦酯的总收率为8.4%,其结构经MS、1HNMR和IR确证。 展开更多
关键词 核苷酸逆转录酶抑制剂 泰诺福韦 富马酸泰诺福韦酯 合成 新合成路线
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HEPT类逆转录酶抑制剂的三维定量构效关系 被引量:14
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作者 孟歌 何严萍 陈芬儿 《高等学校化学学报》 SCIE EI CAS CSCD 北大核心 2002年第7期1304-1308,共5页
利用比较分子力场分析 (Co MFA)方法对 3 2个 HEPT类 HIV-1逆转录酶抑制剂 (RTIs)的三维定量构效关系 (3 D-QSAR)进行了分析 ,建立了 HIV-1逆转录酶抑制剂的 3种 3 D-QSAR模型 ,发现影响其生物活性的主要因素为立体场因素 ,这与 HIV-1 R... 利用比较分子力场分析 (Co MFA)方法对 3 2个 HEPT类 HIV-1逆转录酶抑制剂 (RTIs)的三维定量构效关系 (3 D-QSAR)进行了分析 ,建立了 HIV-1逆转录酶抑制剂的 3种 3 D-QSAR模型 ,发现影响其生物活性的主要因素为立体场因素 ,这与 HIV-1 RT的非底物结合部位 (NNBS)的疏水性环境相吻合 .进一步分析表明 ,适当长度的 1 -位侧链对保持化合物的抗病毒活性致关重要 ;增大 5 -位取代基的体积可增强生物活性 ;在 1 -位苄氧甲基的对位引入大体积基团有利于提高活性 .同时考察立体场、静电场与生物活性的关系 ,表明 ,Co MFA模型 为最佳预测模型 ,其交叉验证系数 R2CV=0 .870 ,传统相关系数 R2 =0 .986,标准偏差SE=0 .1 46,F =2 94.5 46.用此模型预测了检验组 3个 HEPT类化合物的 -lg EC50 ,R2pred=0 .85 0 ,表明模型具有很好的预测能力 ,可为 HEPT类 HIV-1逆转录酶抑制剂的结构优化提供理论指导 . 展开更多
关键词 HEPT类逆转录酶抑制剂 HIV-1逆转录酶抑制剂 比较分子力场分析 三维定量构效关系 抗艾滋病药物
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MMP-9,2,7及其抑制剂TIMP-1,2,3在卵巢肿瘤组织中的表达及临床意义 被引量:10
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作者 胡晓霞 李力 +4 位作者 黎丹戎 张玮 陈心秋 张洁清 唐步坚 《癌症》 SCIE CAS CSCD 北大核心 2004年第10期1194-1198,共5页
背景与目的:基质金属蛋白酶(matrixmetalloproteinases,MMPs)通过降解细胞外基质在肿瘤的侵袭与转移中起着重要作用,MMPs活性又受到其抑制剂(tissueinhibitorofmatrixmetalloproteinase,TIMPs)的调节。本研究通过检测MMP-9、MMP-2、MMP-... 背景与目的:基质金属蛋白酶(matrixmetalloproteinases,MMPs)通过降解细胞外基质在肿瘤的侵袭与转移中起着重要作用,MMPs活性又受到其抑制剂(tissueinhibitorofmatrixmetalloproteinase,TIMPs)的调节。本研究通过检测MMP-9、MMP-2、MMP-7及TIMP-1、TIMP-2、TIMP-3mRNA在卵巢肿瘤组织中的表达,探讨其与卵巢癌临床病理特征和预后的关系。方法:应用RT-PCR方法检测48例卵巢癌、21例良性肿瘤及22例正常卵巢组织中MMP-9、MMP-2、MMP-7及TIMP-1、TIMP-2、TIMP-3mRNA的表达。结果:MMP-9阳性率和MMP-9、MMP-2半定量值在卵巢癌组织中明显高于正常卵巢组织(P<0.05)。TIMP-2、MMP-7、TIMP-3在卵巢恶性及良性肿瘤组织中的阳性率及半定量值明显高于正常卵巢组织。MMP-9/TIMP-1在卵巢癌组织中的比值(0.91±0.67)明显高于正常卵巢组织(0.15±0.34)。MMP-9表达水平与卵巢癌的手术病理分期及预后有关,在Ⅲ~Ⅳ期患者中的表达(1.13±0.66)显著高于Ⅰ~Ⅱ期患者(0.60±0.54)(P<0.05);MMP-9其阳性患者平均生存时间为(43.00±17.12)个月,累积生存率为47.37%,明显低于MMP-9阴性者(100%)。结论:MMP-9、MMP-2、MMP-7、TIMP-2、TIMP-3基因在卵巢恶性肿瘤组织中的表达增加。 展开更多
关键词 MMP-9 卵巢癌 表达水平 MMP-7 TIMP-2 TIMP-1 TIMP-3 RNA 抑制剂 高表达
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喉癌前病变及喉癌中Livin表达的意义及其与Caspase-3表达的关系 被引量:9
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作者 周兰柱 王文忠 +1 位作者 孙哲 吴俊 《中国耳鼻咽喉头颈外科》 CSCD 2016年第3期173-174,共2页
喉癌是呼吸道上皮常见肿瘤,正常上皮由增生开始发展为恶性肿瘤,一般要经过一个量变到质变的过程,即由正常上皮→不典型增生→原位癌,其中包括一个癌前病变阶段,进年来癌前病变的研究已渐成为癌症研究的重点。喉癌前病变包括:喉白斑病... 喉癌是呼吸道上皮常见肿瘤,正常上皮由增生开始发展为恶性肿瘤,一般要经过一个量变到质变的过程,即由正常上皮→不典型增生→原位癌,其中包括一个癌前病变阶段,进年来癌前病变的研究已渐成为癌症研究的重点。喉癌前病变包括:喉白斑病、喉厚皮病、成人喉乳头状瘤、慢性肥厚性喉炎。 展开更多
关键词 喉肿瘤(Laryngeal Neoplasms) 凋亡抑制蛋白质类(inhibitor of Appotosis Proteins) 逆转录聚合酶链反应(reverse transcriptase POLYMERASE Chain Reaction) Caspase-3基因(Caspase-3 Gene)
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抗艾滋病药物的研究进展 被引量:6
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作者 毕毅 徐进宜 吴晓明 《中国现代应用药学》 CAS CSCD 北大核心 2005年第6期461-465,共5页
目的了解目前世界上最新上市的抗艾滋病新药以及正在研究中的新化合物。方法通过对大量有代表性的文献进行归纳,介绍了2000年以来上市的抗艾滋病新药以及各类处于临床和临床前研究的化合物。结果发现抗艾滋病药物在近年来有突破性进展,... 目的了解目前世界上最新上市的抗艾滋病新药以及正在研究中的新化合物。方法通过对大量有代表性的文献进行归纳,介绍了2000年以来上市的抗艾滋病新药以及各类处于临床和临床前研究的化合物。结果发现抗艾滋病药物在近年来有突破性进展,除了传统的蛋白酶抑制剂,逆转录酶抑制剂外,最新发展的融合抑制剂类药物已上市,并且还有很多具有新型作用机制的化合物以及具有抗H IV-1活性的先导天然化合物正处于研究阶段。结论抗艾滋病药物的发展前景广阔。 展开更多
关键词 艾滋病 抗人类免疫缺陷病毒 蛋白酶抑制剂 逆转录酶抑制剂 融合抑制剂
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端粒酶抑制剂联合辐射对人胶质瘤细胞存活的影响 被引量:4
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作者 戴静 周福祥 +4 位作者 肖创映 刘诗权 潘东风 骆志国 周云峰 《武汉大学学报(医学版)》 CAS 2004年第4期447-449,395,共4页
目的 :观察端粒酶抑制剂AZT联合60 Coγ 射线对人脑胶质瘤细胞U2 5 1端粒酶活性及细胞存活的影响 ,探讨AZT的放射增敏作用。方法 :实验分 4组 :A、空白对照组 ;B、放射组 ;C、加药组 ;D、加药放射组。用克隆形成分析法观察AZT对U2 5 1... 目的 :观察端粒酶抑制剂AZT联合60 Coγ 射线对人脑胶质瘤细胞U2 5 1端粒酶活性及细胞存活的影响 ,探讨AZT的放射增敏作用。方法 :实验分 4组 :A、空白对照组 ;B、放射组 ;C、加药组 ;D、加药放射组。用克隆形成分析法观察AZT对U2 5 1细胞放射敏感性的影响 ,通过拟合生存曲线计算放射增敏比SERD0 、SERDq、SERSF2 。用端粒重复序列扩增 (telomericrepeatamplificationprotocol,TRAP) PCR ELISA方法检测端粒酶活性的动态变化。结果 :照射前经 0 .8mmol·L-1AZT处理 2 4h明显降低了 2Gyγ 射线照射后U2 5 1细胞的存活分数 ,SERD0 、SERDq、SERSFM2 分别为 1.2 94 ,1.2 5和 1.36 5 ;表明AZT具有放射增敏的作用 (P <0 .0 5 )。端粒酶活性分析显示A、B、C、D组细胞的端粒酶活性分别为 1.5 6 3± 0 .0 2 2 ,1.92 3± 0 .188,1.0 5 7± 0 .12 6 ,1.2 0 9± 0 .15 3,各组之间差异均有显著性 (P <0 .0 5 )。结论 :AZT能明显抑制 2Gy照射诱导的U2 5 1细胞端粒酶活性升高 ,并显著增加U2 5 1细胞的放射敏感性 ;AZT的放射增敏作用可能与端粒酶活性受抑制有关。 展开更多
关键词 端粒酶 逆转录酶抑制剂 放射敏感性 细胞系 胶质瘤
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