首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 187 毫秒
1.
对氨基二苯醚类似物抑制细胞色素P-450的定量构效关系   总被引:1,自引:0,他引:1  
测定了一组对氨基二苯醚类似物延长小鼠戊巴比妥睡眠时间和体外抑制未经处理的小鼠肝微粒体催化氧化对硝基茴香醚脱甲基的活性。用逐步多元回归分析法导出了这些类似物体内和体外抑制细胞色素P-450(P-450)的活性与量化指数的定量构效关系(QSAR)。结果表明:对氨基二苯醚类似物体内和体外抑制P-450的活性均与最低未占据分子轨道能级(ELUMO)、氨基氮原子的亲核超离域度(SN(N))和醚氧原子的亲核超离域度(SN(O))相关。这些类似物的代谢中间体(MI)与P-450形成P-450代谢中间体络合物(P-450-MI)可能是它们能够抑制P-450的主要原因。  相似文献   

2.
紫杉烷二萜类化合物精细立体结构研究   总被引:2,自引:0,他引:2  
抗肿瘤药物紫杉醇(taxol)是一类新型的纺锤体毒药物。已有的关于紫杉醇及其类似物的构效关系研究表明其分子结构中六元A环的C-13侧链与C4-C5-C20四元氧环对活性有重要贡献。本文研究了紫杉烷二萜类化合物中5/7/6三环骨架C-4取代方式不同的化合物(4个)及6/8/6三环骨架C-4取代方式不同的3类化合物(10个)的晶体结构,阐述了晶态下紫杉烷二萜类化合物因C-4取代方式不同对分子立体结构的影响,从晶体学角度给出6/8/6/4骨架与抗癌活性的关系。  相似文献   

3.
宝藿甙Ⅱ,Ⅲ,Ⅳ,Ⅴ的分离和结构研究   总被引:12,自引:0,他引:12  
李枫  刘永漋 《药学学报》1988,23(9):672-681
自宝兴淫羊藿(Epimedium davidii Franch)全草中分离得十七个黄酮类化合物。确定了E2,E4,E5,E6,E7,E9,E10,E12和E14的化学结构。其中五个为已知成分,即E5为淫羊藿甙-C,E9为淫羊藿甙-A,E12为去甲淫羊藿素,E4为金丝桃甙,E14为山柰素-3-双鼠李糖甙。E2,E6,E7和E10是首次从植物中分离到的黄酮醇甙,分别命名为宝藿甙-Ⅱ,宝藿甙-Ⅲ,宝藿甙-Ⅳ和宝藿甙-Ⅴ。E4和E14在本属植物中系首次发现。  相似文献   

4.
目的 通过对不同工艺下得到的川芎挥发油的比较,阐明提取工艺对其有效成分的影响。方法 分别采用超临界CO2萃取和水蒸气蒸馏法提取川芎挥发油,再通过气相色谱-质谱(GC-MS)联用技术分析鉴定其中的主要化学成分及相对含量。结果 2种方法所得川芎挥发油样品中共鉴定18种共有成分,水蒸气蒸馏提取物中苯酞类成分约占61%,单萜类成分约占25%,倍半萜类成分约占10%;超临界CO2萃取物中苯酞类成分约占97%,单萜类成分约占1%,倍半萜类成分约占0.4%。结论 水蒸气蒸馏法对川芎药材中挥发性较强的单萜和倍半萜类保留相对较强,超临界CO2萃取法对苯酞类有效成分的提取率相对较高,因此在川芎挥发油入药的中药制剂工艺中,应根据制剂的功效充分考虑提取工艺对有效成分的影响。  相似文献   

5.
张万年 《药学学报》1982,17(12):909-916
考虑到适度的吸电子效应载体可以提高三氮烯类抗癌剂的抗癌活性、降低毒性,合成了16个8-三氮烯嘌呤类化合物。全部化合物都进行了抗小鼠L615白血病的筛选,化合物2a、3a、4a和5均有明显的抑制作用,动物生存时间延长300~400%。其中化合物4a的抗癌活性最高,毒性也较低。  相似文献   

6.
核苷类似物是一类重要的抗癌药物。通过在非天然核苷的三氮唑碱基中引入芳香基团,笔者发展了一系列1,2,4-三氮唑核苷类似物。该文简要综述这些三氮唑核苷类似物的分子设计、化学合成及其抗癌活性测试的研究成果。  相似文献   

7.
樟脑胺氯乙酸铂(camphoramine chloroacetic platinum,CCP)是一新的抗癌铂类化合物。本文报道其对小鼠L1210白血病细胞DNA,RNA和蛋白质含量及合成代谢的影响,结果表明、CCP可使细胞内DNA,RNA及蛋白质含量有不同程度的下降,并可明显抑制DNA的合成。采用同位素、荧光探针技术初步分析讨论了CCP对DNA的作用方式。结果提示CCP可能是DNA模板损伤型药物,与DNA发生共价及非共价结合。  相似文献   

8.
用电化学的方法,研究环丙沙星(CPFX)及其镁、锰络合物与脱氧核糖核酸(DNA)的相互作用及其极谱伏安行为。结果在0.1mol·L-1NH3-NH4Cl(pH9.2)溶液中,环丙沙星可与DNA作用,产生一新的极谱峰 Ep=-1.72V(vsAg/AgCl),在有Mg2+或Mn2+存在时则生成三元络合物,产生一电位更负的新峰,峰电位Ep=-1.78V,提示Mg2+或Mn2+离子参与药物与DNA的作用。对它们的还原峰性质研究表明,电极还原反应是完全不可逆的,电流具有吸附性。本文还探讨了电极还原机理,认为参与电极还原的是三元络合物中的环丙沙星分子,进一步推测CPFX-Mg是嵌入DNA的双螺旋结构中。  相似文献   

9.
目的研究1,3-二甲基-4-乙酰基-5-吡唑酮(HL1)的二烃基锡抗癌配合物在近生理条件下与单核苷酸和DNA的作用机制。方法以高分辨核磁共振研究有机锡化合物在不同时间、不同条件下与核苷酸的作用方式并用UV法进一步研究有机锡化合物与DNA的作用。 结果(L1)2SnEt2与AMP作用时可引起AMP碱基上H(8),H(2)和31P峰化学位移值显著变化并可引起DNA增色效应;(L1)2SnMe2与AMP作用时只引起AMP的31P化学位移值的显著变化,未观察到AMP的H(8)和H(2)化学位移值的明显改变,(L1)2SnMe2与DNA的作用可导致DNA的减色效应;(L1)2SnEt2和(L1)2SnMe2在与dCMP和dGMP作用时只引起dCMP和dGMP的31P的化学位移数值的明显变化。结论 3-二甲基-4-乙酰基-5-吡唑酮的二乙基锡配合物(L1)2SnEt2可与AMP的碱基N1和磷酸根氧原子螯合并可能会破坏DNA的双股螺旋结构;而二甲基锡配合物(L1)2SnMe2易与单核苷酸的磷酸氧结合,难以与单核苷酸的碱基氮原子稳定结合且只引起DNA双股螺旋的收缩。  相似文献   

10.
宝藿甙-Ⅰ,Ⅵ,Ⅶ和宝藿素的分离和结构研究   总被引:15,自引:0,他引:15  
李枫  刘永漋 《药学学报》1988,23(10):739-748
自宝兴淫羊藿(Epimedium davidii Franch)中分离出8个黄酮类化合物,根据理化数据、光谱分析(UV,IR,1HNMR,13CNMR,MS)和水解实验证明,其中E3,E13和E8分别为已知成分淫羊藿甙、淫羊藿素和苜蓿素。E1,E11、E16和E15是新黄酮类化合物,并证明结构,分别命名为宝藿甙-Ⅰ(baohuoside Ⅰ),宝藿甙-Ⅵ(baohuoside Ⅵ),宝藿甙-Ⅶ(baohuo side Ⅶ)和宝藿素(baohuosu)。E17的结构待定。  相似文献   

11.
核苷酸还原酶抑制剂抗癌活性与电子结构的关系   总被引:1,自引:0,他引:1  
罗一帆  许旋 《药学学报》1994,29(9):673-679
用CNDO/2量化方法计算了32个异羟肟酸化合物、6个酰胺化合物和9个羧甲酯类化合物的电子结构,对其中的44个化合物的量化指数与其抑制核苷酸还原酶的活性参数PC进行逐步回归计算,得到关于异羟肟酸化合物、酰胺类化合物和羧甲酯类化合物的二个QSAR,由QSAR表明化合物抑制核苷酸还原酶的机制是络合机制。同时,用模式识别方法研究了其中35个化合物的结构对治疗患L1210肿瘤小鼠药效的影响,得到满意的分类图,结果表明化合物的抗癌活性是通过抑制核苷酸还原酶所致,但化合物在体内到达受体的过程和难易程度对药效的影响较大。  相似文献   

12.
We have analysed the effects of 2,3-diepiingol 7,12-diacetate-8-isobutyrate (compound 1 ), ingenol-3-angelate-17-benzoate (compound 2 ), ingenol-3-angelate-17-benzoate-20-acetate (compound 3 ) and 3,5,7,8,9,15-hexahydroxyjatropha-6(17),11-dien-14-one-5,8-bis(2-methylbutyrate)-7-(2-methylpropionate) (compound 4 ), four diterpenes isolated from E. canariensis, on the isometric tension developed by isolated rabbit basilar and carotid arteries. Concentration-response curves to these compounds were obtained cumulatively in both arteries at resting tension and active tone (KCl, 50 mM). At resting tension a concentration-dependent contraction was induced by the four compounds. In the basilar artery the order of potency was 3 = 1 > 2 = 4 , without significant differences between Emax values. In the carotid artery the order of potency was 3 > 2 = 1 = 4 and there were no significant differences between the Emax (maximum effect) values of compounds 1–3 , all of which were higher than that of compound 4 . In pre-contracted basilar artery compounds 1–3 induced concentration-dependent relaxation and compound 4 was almost ineffective; the order of potency was 3 > 2 = 1 without significant differences between Emax values. In the carotid artery with active tone the four compounds tested induced further contractions; the order of potency was 3 > 2 = 4 > 1 without significant differences between Emax values. These results show that the four diterpenes are potent active substances in rabbit basilar and carotid arteries and that there are regional differences between their action. The four compounds tested contract basilar and carotid arteries at resting tension. Compounds 1–3 relax pre-contracted basilar artery but not carotid artery.  相似文献   

13.
14.
15.
本文用 CNDO 分子轨道法计算了靛玉红及其异构体、衍生物和核酸中嘌呤碱的分子轨道能级和系数。在此基础上,提出了计算靛玉红类药物与受体鸟嘌呤之间络合价的新研究方法。用该法算得的药物与受体之间的络合价与这些药物的抗肿瘤活性成很好的并行关系。这就为探明靛玉红类药物的抗肿瘤机理和构效关系提供了明确而具体的信息。最后还讨论了该类药物选择性地与 RNA 肿瘤病毒的单链 RNA 中的鸟嘌呤发生π—电荷转移络合作用的抗肿瘤机理和计算络合价法在以核酸为作用目标的新药分子设计中的意义。  相似文献   

16.
The synthesis of some new (E)-6-[2-(furan-2-yl)ethenyl]-1,2,4-triazin-5-ones directly linked to either pyrazole, pyrazoline, pyrazolidine counterparts, or to substituted thio and hydrazono functionalities is described. Six of the newly synthesized compounds were selected by the National Cancer Institute (NCI) to be evaluated for their in vitro antitumor activity according to the protocol of the NCI in vitro disease-oriented human cells screening panel assay. The results revealed that the pyrazole derivative 5c was found to be the most active member in this screen as evidenced by its ability to exert potential growth inhibitory activity against most of the tested subpanel tumor cell lines with selective influence on leukemia subpanel tumor cell lines (GI50 values 2.01–3.03 μM). Moreover, a comparative study for log GI50 values of both compound 5c and 5-fluorouracil (5-FU) revealed that compound 5c showed higher potency than 5-FU against most of the tested subpanel tumor cell lines. Thus compound 5c could be considered as a suitable lead towards the design of broad spectrum antitumor active agents targeting various human tumor cell lines.  相似文献   

17.
Neurodegenerative disorders are consequences of progressive and irreversible loss of neurons due to unwanted apoptosis, which involves caspases, a group of cystein proteases that cleave other proteins and inactivate them. Among several different groups of caspase enzymes, caspases-3 play a key role in apoptosis. Therefore they are used as therapeutic target for their inhibitors. In pursuit of better caspase-3 inhibitors, a quantitative structure–activity relationship analysis was performed on a series of 1,3-dioxo-4-methyl-2, 3-dihydro-1H-pyrrolo [3,4-c] quinolines as caspase-3 inhibitors using WIN CAChe 6.1 and Medicinal Chemistry Regression Machine. The best QSAR model was selected and validated. The values of the statistical data are r = 0.951, F = 65.62, SEE = 0.4175, t = 2.08. The study reveals that, if the partition coefficient (log P), conformational minimum energy (CME), and the lowest unoccupied molecular orbital energy (E LUMO) are altered, the biological activity is increased. On the basis of the selected QSAR model, we designed a new series of compounds, calculated their activity, and found that the compounds were more potent than existing compounds.  相似文献   

18.
19.
20.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号