新抗癌有效成分海南粗榧内酯(Hainanolide)结构的研究

自海南粗榧树皮中分离出两种新的化合物即海南粗榧内酯和海南粗榧内酯醇,海南粗榧内酯是一种新抗癌有效成分。动物试验结果表明对L₆₁₅、S₁₈₀、Lewis肺癌P₃₈₈和L₁₂₁₀均显活性。根据X-衍射分析、核磁共振谱、红外光谱、紫外光谱、旋光光谱和质谱等证明海南粗榧内酯是一种新的结构类型的抗癌化合物,其结构式为Ⅰ。海南粗榧内酯醇的结构与海南粗榧内酯的结构很相似,其结构的研究正在进行中。     

海南粗榧内酯(Hainanolide)的抗病毒作用

海南粗榧内酯是从海南粗榧树皮中分离出的一种新的活性成分,结构式如下。它是一种含有革酮环的内酯类化合物。据报道对动物肿瘤L_(615)、S_(180)、W_(256)、Lewis肺癌、P_(388)以及     

海南粗榧内生真菌S26化学成分研究

目的对海南粗榧内生真菌S26发酵液的化学成分进行研究。方法用多种柱色谱技术对化合物进行分离纯化,根据波谱数据和理化性质鉴定化合物的结构。结果从海南粗榧内生真菌S26的发酵液中分离得到6个化合物,分别鉴定为（-）-5-methylmellein（1）、（-）-3,5-dimethyl-8-methoxy-3,4-dihydroisocoumarin（2）、ergosterol peroxide（3）、（3β,5a,8a,22E,24R）-5,8-epidioxy-ergosta-6,9（11）,22-trien-3-ol（4）、22E,24R—ergos—ta-7,22-diene-3β,5α,6β,9α-tetraol（5）、对羟基苯乙醇（6）。结论以上化学成分为从海南粗榧内生真菌中首次分离得到。     

海南粗榧新碱衍生物HH07A在大鼠体内的代谢转化研究

用GC-MS联用技术对海南粗榧新碱衍生物HH07A在大鼠体内代谢转化进行了研究。尿样经XAD-2固相提取、酶水解、浓缩并硅烷化,用GC-MS联用仪分离鉴定尿中HH07A及其4个代谢物,推断4个代谢物结构及其体内代谢途经。     

海南粗榧中的苯丙素类化合物及其抗氧化活性

目的对海南粗榧的化学成分进行研究。方法采用多种色谱技术进行化合物的分离纯化，利用光谱技术和理化性质鉴定化合物的结构。采用DPPH法进行抗氧化活性测试。结果从海南粗榧的乙醇提取物中分离得到3个苯丙素类化合物，分别鉴定为junipediol A（1）、junipediol A 8-O-β-D-glucopyranoside（2）和junipediol B（3）。结论化合物1～3均为首次从该属植物中分离得到，3个化合物均具有抗氧化活性。     

三尖杉中抗癌有效成分—海南粗榧内酯的分离和鉴定

前已报道,从海南粗榧(Cephalotaxus hainanensis Li)树皮中分离得到海南粗榧内酯(Hainanolide),并测定了它的结构。 海南粗榧内酯对L_(615)、S_(180)、W_(256)、Lewis肺癌、P_(388)和L_(1210)均有活性。这是一种新类型的抗癌活性成分,在药物化学和寻找新抗癌药物的工作中是很值得注意的。Buta等从同属植物Cephalotaxus harringtonia的种子中分得相同的化合物,测定了结构,命名为Harringtonolide,并发现具有抑制植物生长的作用,但未报道有抗癌活性。     

雷公藤叶中二萜化合物的研究

从雷公藤(Tripterygium wilfordii)叶中分离出九个二萜化合物,经物理常数测定、化学反应、以及波谱数据分析,分别鉴定为雷公藤内酯酮(triptonide,1)、雷公藤内酯醇(triptolide,2)、雷公藤内酯二醇(tripdiolide,3);雷醇内酯(triptolidenol,4)、16-羟基雷公藤内酯醇(16-hydroxytriptolide,5)、雷公藤氯内酯醇(tripehlorolide,6)、雷藤内酯三醇(triptriolide,7),以及新化合物雷公藤内酯二醇酮(tripdiotolnide,8)和13,14-环氧9,11,12-三羟雷公藤内酯(13,14-epoxide 9,11,12-trihydroxytriptolide,9)。新化合物的生物活性正在研究。     

月桂氮(艹卓)酮对灭痤乳膏中螺内酯透皮作用研究

目的：研究不同浓度的月桂氮卓酮对灭痤乳膏中螺内酯小鼠离体皮肤渗透性的影响。方法：用改良的Franz扩散池，不同浓度月桂氮卓酮(0、1％、2％和5％)作促渗性试验，采用HPLC法测定和计算药物累积释放量(Q)，稳态流量（J），渗透系数(Kp)。结果：含1％～5％月桂氮卓酮的灭痤乳膏中螺内酯的Q值，较不含月桂氮卓酮者增加了73.66％～74.61％，但各浓度间Q值无显著性差异。结论：1％～5％月桂氮卓酮对灭痤乳膏中螺内酯有明显促渗作用。     

水溶性月桂氮(艹/卓)酮对达克罗宁粘膜促渗作用的药效学研究

目的 :考察月桂氮艹卓 酮的粘膜促渗作用。方法 :以达克罗宁为模型药 ,用青蛙和蚯蚓试验法分别研究了月桂氮艹卓 酮对达克罗宁麻醉效果的影响。结果 :与不含月桂氮艹卓 酮的样品比较 ,体积分数为 1 %的月桂氮艹卓 酮能显著促进达克罗宁的粘膜渗透作用 (P <0 .0 1 ) ,短麻缩醉的潜伏期 ;用 0 .5%的月桂氮艹卓 酮作促渗剂 ,可使达克罗宁的麻醉作用效价强度提高 3倍。结论 :考察了月桂氮 艹卓 酮对达克罗宁粘膜促渗作用的影响 ,其结果为进一步研究月桂氮艹卓 酮在透皮给药系统方面的应用提供了有益的参考     

三尖杉中的微量生物碱

自分离海南粗榧内酯和海南粗榧新碱后剩余的三尖杉Cephalotaxus fortunei Hook.f.的弱碱部分,又分出了5种微量生物碱(碱Ⅰ～Ⅴ)。碱Ⅱ和Ⅴ分别鉴定为3-表甲基西哈灭里辛碱B(3-epimethylscheIhammericine B和3-表西哈灭里辛碱3-epischelhammericine,均为首次报道存在于三尖杉中。碱Ⅲ鉴定为异三尖杉酮碱isocephalotaxinone,系首次自植物中分得。碱Ⅳ是一种新生物碱,根据物理常数和光谱分析,推定其结构如Ⅳ所示,命名为表福建三尖杉碱2-epicephal of ortuneine)。碱Ⅰ的结构待进一步研究。     

Characteristic molecular packing in the crystal structure of tert-butoxycarbonyl-L-phenylalanyl-L-methionine methyl ester

The molecular conformation and association of the peptide Boc-L-Phe-L-Met-OMe have been studied in the solid state by X-ray diffraction. The peptide crystallizes in the orthorhombic system, space group P2₁2₁2₁, with cell parameters of a= 9.821(2), b= 25.394(6), c= 28.714(8) ų, V= 7161(3) ų. The structure has been solved by direct methods and refined to a final R of 0.079 for 5464 independent reflections with F_o≥σ(F_o). The crystal consists of three independent molecular conformations per asymmetric unit. Respective peptide backbones adopt an extended conformation with the side-chains of Phe and Met residues being arranged below and above the backbone chains. Contrary to the sheet structure most frequently observed in the crystal packing of the extended peptide conformations, three independent molecules lie spirally along the c-axis and form a pin-wheel-like crystal packing. The sheet structures formed by two of three independent molecules are almost at right angles to the backbone of the remaining molecule. This molecular packing mode would provide a possible interaction model between the intersecting β-sheet structure and single-strand structure of polypeptide. © Munksgaard 1994.     

Conformation of arginine side chain in a mini peptide. Molecular structure of acetyl-l-arginine-ethylamide

The crystal structure of N-α-acetyl-l -arginine ethylamide perchlorate (molecular formula: C₁₀H₂₁N₅O₂ ± HClO₄) has been determined from X-ray diffraction data. This arginine derivative has the two charged ends substituted by peptide units and thus becomes representative of an arginyl residue in a protein. The crystals are orthorhombic, space group P2₁,2₁,2₁, a = 7.485 (2), b = 28.623 (5), c = 7.261 (3) Å, Z = 4. The structure was solved by direct methods and refined by full matrix least-squares using 559 reflections to an R = 0.052. The molecule shows two planar peptide units with φ and ø values in the β pleated sheet region. The side chain torsion angles are in trans conformation, except the χ₁, angle which is in the gauche(-) region. This observation further illustrates that this is one of the favoured side chain conformations of arginine, together with the all-trans conformation. Symmetric double hydrogen bonds are observed between the guanidinium group and perchlorate anions. The H(N) and oxygen atoms of the amide groups also form hydrogen bonds.     

Complete primary structure of statherin,a potent inhibitor of calcium phosphate precipitation,from the saliva of the monkey,Macaca arctoides

Human saliva, which is supersaturated with respect to basic calcium phosphate salts, is stabilized primarily by the presence of two classes of phosphoproteins, statherin and the acidic proline-rich proteins (PRP). These molecules act by inhibiting both primary (spontaneous) precipitation of calcium phosphates in saliva and secondary (surface induced) precipitation of these salts onto dental enamel. The complete amino-acid sequences of several human PRP and the N-terminal sequence of PRP from saliva of M. arctoides have been determined. Similarly, the complete sequence of statherin from human and M. fascicularis saliva is known. We now report the complete structure of statherin from the saliva of the stump-tailed monkey, M. arctoides. The structure was determined by gas-phase sequencing of intact statherin, elucidating positions 1-26, and sequencing an unpurified mixture of tryptic peptides which elucidated the remaining positions through the C-terminus (residue 42) of the molecule. This latter degradation produced an eight amino-acid overlap with that of intact statherin and was confirmed by C-terminal analysis and amino-acid composition of native statherin. The complete amino-acid sequence of M. arctoides statherin is: NH₂-Asp-PSer-PSer-Glu-Glu₅-Lys-Phe-Leu-Arg-Arg₁₀-Leu-Arg-Arg-Phe-Asp₁₅-Glu-Gly-Arg-Tyr-Gly₂₀-Pro-Tyr-Gln-Pro-Phe₂₅-Val-Pro-Pro-Pro₂₉Leu₃₀-Tyr-Pro-Gln-Pro-Tyr₃₅-Gln-Pro-Tyr-Gln-Pro₄₀ -Gln-Tyr-COOH This sequence differs from human statherin at positions 11, 12, 15, 16, 18, 25-27, 38-40 and from M. fascicularis statherin at positions 26 and 28.     

Crystal structure of neotame anhydrate polymorph G

Purpose. To determine the crystal structure of the neotame anhydrate polymorph G and to evaluate X-ray powder diffractometry (XRPD) with molecular modeling as an alternative method for determining the crystal structure of this conformationally flexible dipeptide. Methods. The crystal structure of polymorph G was determined by single crystal X-ray crystallography (SCXRD) and also from the X-ray powder diffraction (XRPD) pattern using molecular modeling (Cerius² , Powder Solve module). Results. From SCXRD, polymorph G crystals are orthorhombic with space group of P2₁2₁2₁ with Z = 4, unit cell constants: a = 5.5999(4), b = 11.8921(8), c = 30.917(2) Å, and one neotame molecule per asymmetric unit. The XRPD pattern of polymorph G, analyzed by Cerius² software, led to the same P2₁2₁2₁ space group and almost identical unit cell dimensions. However, with 13 rigid bodies defined, Cerius² gives a conformation of the neotame molecule, which is different from that determined by SCXRD. Conclusions. For neotame anhydrate polymorph G, the unit cell dimensions calculated from XRPD were almost identical to those determined by SCXRD. However, the crystal structure determined by XRPD closely resembled that determined by SCXRD, only when the correct conformation of the neotame molecule had been chosen before detailed analysis of the XRPD pattern.     

(R)-(+)-脱水芽子碱甲酯的合成工艺研究及结构表征

目的对(R)-(+)-脱水芽子碱甲酯的合成工艺进行研究和结构表征。方法以托品酮为原料,经克莱森缩合、拆分、还原和消除得到目标产物,并以成盐的方式得到其富马酸盐,以溶剂挥发法培养单晶,采用X射线单晶衍射对结晶形态进行表征。结果优化了合成工艺,总收率为36%。测试结果表明不对称单位化学计量式为C_(14)H_(19)NO_6,相对分子质量为297.30,晶体密度为1.359 g/cm~3,该晶胞属于正交晶系,空间群为P2_12_12_1。结论本合成工艺简化了实验操作,更适合大规模制备,且为脱水芽子碱的结构确证提供了新的依据。     

Synthesis,Antibacterial Activities,and 3D‐QSAR of Sulfone Derivatives Containing 1, 3, 4‐Oxadiazole Moiety

A series of sulfone derivatives containing 1, 3, 4‐oxadiazole moiety were prepared and evaluated for their antibacterial activities by the turbidimeter test. Most compounds inhibited growth of Ralstonia solanacearum (R. solanacearum) from tomato and tobacco bacterial wilt with high potency, among which compounds 5a and 5b exhibited the most potent inhibition against R. solanacearum from tomato and tobacco bacterial wilts with EC₅₀ values of 19.77 and 8.29 μg/mL, respectively. Our results also demonstrated that 5a, 5b , and a number of other compounds were more potent than commercial bactericides Kocide 3000 and Thiodiazole Copper, which inhibited R. solanacearum from tomato bacterial wilt with EC₅₀ values of 93.59 and 99.80 μg/mL and tobacco bacterial wilt with EC₅₀ values of 45.91 and 216.70 μg/mL, respectively. The structure–activity relationship (SAR) of compounds was studied using three‐dimensional quantitative structure–activity relationship (3D‐QSAR) models created by comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) based on compound bioactivities against tomato and tobacco bacterial wilts. The 3D‐QSAR models effectively predicted the correlation between inhibitory activity and steric–electrostatic properties of compounds.     

Macrocyclic inhibitors of HCV NS3 protease

Background: HCV NS3 is a serine protease that plays a pivotal role in catalyzing the cleavage of the single polyprotein encoded by HCV after infection of hepatocytes. Analysis of the X-ray crystal structure of the enzyme reveals a shallow catalytic site located on the surface of the protein, which has made development of inhibitors a formidable task. Attempts to discover leads by a traditional approach of screening of compound libraries have proved futile and, therefore, researchers have adopted a structure-based drug design. Analysis of the X-ray structure of NS3 protease reveals close proximity of S₁-S₃ and S₂-S₄ pockets. Various novel approaches have been used to design preorganized, depeptidized macrocyclic inhibitors linking the P₂-P₄ groups and P₁-P₃ residues. Objective: The article summarizes efforts by various groups to develop inhibitors that bind to the active site and inhibit viral replication. Method: Review of recent patents and scientific literature. Conclusion: Macrocyclization has proved to be an effective tool for depeptidization of peptidic inhibitors with improved binding and pharmacokinetic properties.     

Crystal structure of L-lysyl-L-glutamic acid dihydrate

L-Lysyl-L-glutamic acid dihydrate, C₁₁N₃O₅H₂₁·2H₂O, crystallizes in the monoclinic space group P2₁ with a = 12.474(2), b = 5.020(1), c = 13.157(2) Å, β= 114.69(1)° and Z = 2. The crystal structure was solved by direct methods and refined to an R value of 0.037 using full matrix least-squares method. The molecule exists as a double zwitterion with both the amino and carboxyl groups ionised. The peptide has a folded conformation with its Lys residue trans and Glu residue gauche^?gauche⁺. The side chains of the Lys and Glu residues correspond to all trans and folded (g^?g^?g^?) conformations respectively. The terminal carboxyl group forms hydrogen bonds with the ξ-amino group of the lysine side chain. The head-to-tail interaction often seen in peptide crystals is absent in the present structure. In the extended crystal structure water molecules form channels along the b direction and are enclosed within helically arranged hydrogen bonds formed by the lysine side chain and the peptide backbone.     

Effects of a new antiarrhythmic compound SUN 1165 [N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride] on the sodium currents in isolated single rat ventricular cells

Summary The effects of a new antiarrhythmic compound, SUN 1165 (which resembles lidocaine in chemical structure) on sodium currents (I _Na) of enzymatically isolated, single rat ventricle cells were studied under current or voltage clamp conditions. A suction pipette technique was used for current injection and internal perfusion. Potassium currents were blocked by replacing K⁺ with Cs⁺ in the internal and external solutions, and calcium current by replacing Ca²⁺ with Co²⁺ in the external solution. When cells were stimulated infrequently (<1 Hz), SUN 1165 decreased I _Na without changing the position of the current-voltage curve. The inactivation curve of I _Na shifted to negative potentials along the voltage axis. The drug also produced an additional use-dependent block of I _Na, which depended on the frequency of the voltage clamp pulse. The effects of SUN 1165 on I _Na resemble those of lidocaine, although the relative importance of use-dependent action versus tonic blockade differs from that of lidocaine.