绿藻硫酸多糖UCS2的结构及抗凝血活性研究

目的 对绿藻多糖UCS2的结构特征和抗凝血活性进行研究。方法 通过冷水提取、强阴离子交换色谱和凝胶渗透色谱,从绿藻花石莼中提取分离得到硫酸多糖UCS2;采用高效凝胶渗透色谱（HPGPC）、高效液相色谱、红外光谱和气质联用色谱对多糖UCS2的结构进行表征;通过活化部分凝血活酶时间（APTT）、凝血酶时间、凝血酶原时间对多糖UCS2体外抗凝血活性进行研究。结果 绿藻多糖UCS2分子量为39.55kDa,硫酸根和糖醛酸含量分别为19.74%和18.66%;UCS2主要由鼠李糖组成,含有少量葡糖醛酸和木糖。糖链中含有→3,4)-α-L-Rhap-(1→, →4)-α-L-Rhap-(1→, →4)-β-D-Xylp-(1→和→4)-β-D-GlcAp-(1→,硫酸基位于→4)-α-L-Rhap-(1→的C-3位。多糖UCS2对APTT有显著延长作用,具有较高的抗凝活性。结论 绿藻多糖UCS2是1种抗凝活性的葡萄糖醛酸-木糖-鼠李糖型硫酸多糖。     

1种绿藻硫酸多糖的化学组成及其结构研究

目的 对1种绿藻硫酸多糖的化学组成及其结构特征进行研究。方法 通过热水提取法,从1种石莼属海藻中提取硫酸多糖,采用强阴离子交换色谱和凝胶渗透色谱对多糖进行分离纯化;采用高效凝胶渗透色谱(HPGPC)、高效液相色谱以及化学方法对多糖的纯度、分子量、单糖组成和化学成分进行分析测定;通过红外光谱和气质联用方法对多糖的结构进行表征。结果 多糖HP2S在HPGPC色谱图上呈单一对称峰,分子量为90.5 kDa,硫酸根和糖醛酸含量分别为32.1%和7.4%,HP2S主要由鼠李糖组成,含有少量葡萄糖、葡萄糖醛酸、半乳糖和木糖,HP2S糖链中鼠李糖主要存在形式为(1→2)-Rhap 、(1→3)-Rhap 和(1→2, 3)-Rhap,硫酸根位于(1→3)-Rhap 的C-2位或(1→2)-Rhap 的C-3位上。结论 水溶性多糖HP2S是1种结构新颖的主要由鼠李糖组成的硫酸化多糖。     

海洋硫酸多糖PAE的结构和抗病毒活性研究

目的 对肠浒苔来源的硫酸多糖的结构和抗病毒活性进行研究。 方法 通过稀碱提取法,从肠浒苔中提取硫酸多糖,采用强阴离子交换色谱和凝胶渗透色谱对多糖进行分离纯化;采用高效液相色谱(HPLC)、高效凝胶渗透色谱(HPGPC)、傅里叶变换红外光谱(IR)以及气质联用色谱(GC-MS)方法对多糖的结构进行表征;采用细胞病变效应测定PAE对不同病毒的抑制率。 结果 从肠浒苔中分离得到多糖PAE,其分子量为13.98 kDa,主要由鼠李糖、葡萄糖醛酸和木糖构成,糖链主要由(1→4)-Rhap,(1→3,4)-Rhap,(1→2,4)-Rhap,Xylp(1→和(1→4)-Glcp组成,硫酸根主要位于(1→4)-Rhap 的C-2或C-3位以及Xylp(1→的C-4位上,PAE具有良好的抗病毒活性,特别是对呼吸道合胞体病毒的抑制率较高。 结论 海洋多糖PAE是一种结构新颖的由鼠李糖、葡萄糖醛酸和木糖组成的硫酸多糖,具有良好的抗病毒活性。     

绿藻硫酸多糖SHW及其低分子量片段的结构及抗凝活性研究*

目的 对绿藻多糖SHW及其低分子量片段的结构及抗凝活性进行研究。方法 通过热水提取、强阴离子交换色谱和凝胶渗透色谱,从绿藻硬毛藻中提取分离得到硫酸多糖SHW;通过可控酸解方法制备SHW低分子量片段;采用高效凝胶渗透色谱、高效液相色谱、红外光谱及甲基化方法对多糖结构进行表征;通过活化部分凝血活酶时间、凝血酶时间、凝血酶原时间研究多糖SHW及其低分子量片段体外抗凝血活性。结果 多糖SHW及其低分子量片段主要由阿拉伯糖组成,含有少量半乳糖和氨基葡萄糖;糖链中阿拉伯糖主要以→4)-Arap-(1→和→3,4)Arap-(1→的形式存在,半乳糖以→4)-Galp-(1→存在形式,硫酸根主要位于→4)-Arap-(1→的C-3位。SHW及其低分子量片段A1～A6的分子量分别为492 kDa、200 kDa、170kDa、100kDa、26kDa、14kDa 和10 kDa。SHW 具有较高的抗凝血活性,且其抗凝活性随着其分子量的减少而降低。结论 海藻多糖SHW是一种具有抗凝活性的新颖硫酸多糖,其抗凝活性与分子量密切相关。     

沙蚕(Perinereis aibuhitensis)硫酸多糖的结构表征及抗凝血活性研究

目的 对来源于沙蚕（Perinereis aibuhitensis）的硫酸多糖进行结构表征和抗凝血活性研究。方法 采用两步酶解法从沙蚕中提取多糖;利用强阴离子交换色谱和凝胶渗透色谱对粗多糖进行分离纯化;通过离子色谱法、高效液相色谱法（HPLC）、高效凝胶渗透色谱-多角度激光光散射仪（HPGPC-MALLs）联用技术、硫酸软骨素酶ABC酶法分析、核磁共振氢谱（1H-NMR）等方法,研究纯化多糖的化学组成和结构特征;通过测定APTT、PT和TT评价其体外抗凝血活性。结果 从沙蚕中纯化得到了2种硫酸多糖组分PAE1和PAE2,二者的总糖含量、蛋白含量、硫酸根含量及分子量分别为65.21%、14.31%、0.33%、24.49 kDa和53.08%、11.33%、13.46%、57.39 kDa。PAE1主要由Gal（43.58%）、Glc（32.63%）、GalN（8.71%）、GlcA（7.66%）及少量Fuc（2.77%）组成;PAE2主链为硫酸软骨素C（GlcAβ1→3GalNAc6S）,支链主要由Fuc（35.33%）、Gal（20.9%）和Glc（8.98%）构成。PAE1和PAE2均可明显延长APTT和PT。结论 首次从沙蚕中提取、分离得到2种硫酸多糖,其中PAE2是1种含有Fuc、Gal与Glc支链并具有明显的体外抗凝血活性的结构新颖的类硫酸软骨素,该发现为沙蚕硫酸多糖的开发提供了依据。     

褐藻中岩藻聚糖硫酸酯抗凝血活性研究

目的对褐藻中岩藻聚糖硫酸酯的抗凝血活性进行研究。方法将20只新西兰白兔随机分为2组：岩藻聚糖硫酸酯组和空白对照组，分别测定其APTT、PT和TT。结果岩藻聚糖硫酸酯组和空白对照组APTT测定分别为62．7±11．3（s）、35．6±9．7（s），P〈0．05，差别有显著性意义；PT测定分别为19．5±4．8（s）、13．4±4．7（s），P〈0．05，差别有显著意义；TT测定分别为39．3±9．8（s）、21．5±7．3（s），P〈0．05，差别有显著性意义。结论褐藻中岩藻聚糖硫酸酯具有显著的抗凝血活性。     

抗凝血活性海洋硫酸多糖HP1-1的结构研究

目的 对抗凝血活性海洋硫酸多糖HP1-1的结构进行研究。方法 通过高效液相色谱(HPLC)、高效凝胶渗透色谱(HPGPC)、傅里叶变换红外光谱(IR)以及气质联用色谱(GC-MS)和核磁共振波谱(NMR)方法,对抗凝血活性海洋硫酸多糖HP1-1的结构进行解析。结果 海洋硫酸多糖HP1-1的分子量为297 kDa,总糖和硫酸基含量分别为78.1%和12.3%;HP1-1主要由葡萄糖组成,含有少量半乳糖、阿拉伯糖和甘露糖;HP1-1糖链中含有→4)-Glcp-(1→、→3)-Glcp-(1→、→3,4)-Glcp-(1→、→4)-Arap-(1→、→3,4)-Galp-(1→和→3)-Galp-(1→,硫酸基位于→4)-Glcp-(1→的C-3位和→3)-Galp-(1→的C-4位。 结论 海洋多糖HP1-1是主要由葡萄糖组成的硫酸多糖,含有多种糖基连接方式,为独特结构序列的新颖海洋硫酸甘露阿拉伯半乳葡聚糖。     

不同部位变黑雷松藻（Lessonia nigrescence)多糖的结构及其抗凝活性比较研究

目的 从变黑雷松藻（Lessonia nigrescence）的根部和茎部中分别提取分离得到2种褐藻胶(LNA1, LNA2)与2种褐藻糖胶(LNF1,LNF2),在对其进行理化性质和结构分析基础上,进一步对其抗凝活性进行评价。方法 运用纤维素膜电泳（CME）、高效凝胶渗透色谱（HPGPC）、高效液相色谱（HPLC）对4种多糖进行纯度、分子量和单糖组成分析;采用红外光谱（IR）和核磁共振氢谱（1H-NMR）对4种多糖进行结构分析;通过活化部分凝血活酶时间（APTT）和凝血酶原时间（PT）评价4种多糖抗凝活性。结果 根部褐藻胶中甘露糖醛酸含量（73 %）明显高于颈部（61 %）,LNF1和LNF2均是以岩藻糖、木糖和半乳糖为主的硫酸岩藻聚糖,均能显著延长APTT,但对PT影响较小。结论 变黑雷松藻根部褐藻胶中甘露糖醛酸含量明显高于茎部,褐藻糖胶中的硫酸酯基主要存在于岩藻糖的C4和C2/C3位,且主要通过影响内源凝血途径发挥抗凝作用。     

硫酸酯化螺旋藻酸性多糖的气相色谱中不同衍生化方法的比较

为测定硫酸酯化螺旋藻酸性多糖单糖组成及摩尔比，并比较不同的衍生化方法的优劣，先后采用糖腈乙酸酯衍生、糖醇乙酸酯衍生及气相色谱同时测定醛糖和糖醛酸3种衍生方法，分别进行气相色谱分析。结果：硫酸酯化螺旋藻酸性多糖由甲基化鼠李糖、鼠李糖、核糖、葡萄糖及半乳糖醛酸组成，其摩尔比为4：6．5：2：3：1。糖腈乙酸酯衍生方法简单、操作简便，糖醇乙酸酯衍生及气相色谱同时测定醛糖和糖醛酸2种方法定量结果十分接近。     

纤维素硫酸酯体内抗凝血活性的实验研究

目的:研究纤维素硫酸酯对动物体内的抗凝血活性。方法:用试管法测凝血时间(CT),用凝固法测定活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)和凝血酶时间(TT),以肝素和硫酸化右旋糖酐为阳性对照,考察其抗凝血活性的量效性和时效性。结果:纤维素硫酸酯能显著延长CT,APTT和TT,且呈剂量依赖性,但在所试剂量范围内对PT无明显影响;其抗凝血活性在给药2h时达到最大。结论:纤维素硫酸酯具有明显抗凝血作用,强于现有同类抗凝血药硫酸化右旋糖酐,略低于150IU·mg-1的肝素。     

Pharmacological study on piperine

Systematic pharmacological studies on piperine have revealed that this compound elicited diverse pharmacological activities; CNS depressant activity characterized by antagonism against electroshock seizure and by muscle relaxant activity in mice; antipyretic activity in typhoid vaccinated rabbits; analgesic activity as evaluated by tail-clip pressure and writhing syndrome in mice; antiinflammatory activity in carrageenin-induced edema in rats.     

Synthesis of new thiazolylthiazolidinylbenzothiazoles and thiazolylazetidinylbenzothiazoles as potential insecticidal, antifungal, and antibacterial agents

A series of 2-{[2'-(3'-chloro-2'-oxo-4'-substitutedaryl-1'-azetidinyl)-1',3'-thiazol-4'-yl] thio}benzothiazoles (4a-4e) and 2-{[(2'-(2'-substitutedaryl-4'-thiazolidinon-3'-yl)-1',3'-thiazol-4'-yl]thio}benzothiazoles (5a-5e) have been synthesized from 2-[(2'-substitutedarylidenylimino-1',3'-thiazol-4'-yl)thio]benzothiazoles (3a-3e). The structure of these compounds has been elucidated by elemental (C, H, N) and spectral (IR, (1)H-NMR, Mass) analysis. Furthermore, compounds 3a-3e, 4a-4e, and 5a-5e were screened for insecticidal activity against Periplaneta americana and antifungal, antibacterial activities in vitro against different strains of fungi and bacteria. Out of the fifteen compounds tested, compound 5b, 2-{[2'-(2'-p-hydroxy-m-methoxyphenyl)-4'-thiazolidinon-3'-yl)-1',3'-thiazol-4'-yl]thio}benzothiazole, was found to possess most prominent insecticidal activity.     

Juniperus oxycedrus L. subsp. oxycedrus and Juniperus oxycedrus L. subsp. macrocarpa (Sibth. & Sm.) Ball. “berries” from Turkey: Comparative evaluation of phenolic profile,antioxidant, cytotoxic and antimicrobial activities

This work aimed to evaluate and compare the phenolic profile and some biological properties of the ripe “berries” methanol extracts of Juniperus oxycedrus L. subsp. oxycedrus (Joo) and Juniperus oxycedrus L. subsp. macrocarpa (Sibth. & Sm.) Ball. (Jom) from Turkey. The total phenolic content resulted about 3-fold higher in Jom (17.89 ± 0.23 mg GAE/g extract) than in Joo (5.14 ± 0.06 mg GAE/g extract). The HPLC–DAD–ESI–MS analysis revealed a similar flavonoid fingerprint in Joo and Jom, whereas a difference in their quantitative content was found (4632 μg/g extract and 12644 μg/g extract). In addition, three phenolic acids were detected in Jom only (5765 μg/g extract), and protocatechuic acid was the most abundant one. The antioxidant capacity of the extracts was evaluated by different in vitro assays: in the DPPH and in the TBA tests a stronger activity in Jom was highlighted, while Joo exhibited higher reducing power and metal chelating activity. Joo and Jom did not affect HepG2 cell viability and both extracts resulted virtually non-toxic against Artemia salina. The extracts were also studied for their antimicrobial potential, displaying efficacy against Gram-positive bacteria.     

Structure-antibacterial,antitumor and hemolytic activity relationships of cecropin A-magainin 2 and cecropin A-melittin hybrid peptides

In order to elucidate the structure-antibiotic activity relationship of cecropin A-magainin 2 and cecropin A-melittin hybrid peptides, several truncated peptides and the analogues with amino acid substitutions were synthesized and their antibacterial, antitumor and hemolytic activities of were examined. Cecropin A-magainin 2 hybrid analog, L¹⁶-CA(1–8)-MA(1–12) (termed as L-CA-MA in this study: KWKLFKKIGIGKFLHLAKKF-NH₂), is known to have potent antibacterial and antitumor activity with less hemolytic activity. We found that the C-terminal region of L-CA-MA is more involved in the α-helical structure on cell membrane-like environment than N-terminal one by circular dichroism analysis. Deletion of the Gly-lle-Gly sequence, the central hinge region of L-CA-MA, produced a considerable reduction in antitumor and hemolytic activity rather than an antibacterial one. The insertion of Pro, Gly-lle or Gly-Pro in this hinge region of L-CA-MA caused retention of both antibacterial and antitumor activity while causing a significant decrease in hemolytic activity. However, the substitution with Gly-Pro-Gly instead of the Gly-lle-Gly in CA(1–8)-MA(1–12), CA(1–8)-ME(1–12), CA(1–13)-MA(1–13) and CA(1–13)-ME(1–13) hybrids resulted in a drastic decrease in antibacterial, antitumor and hemolytic activity. The increase of hydrophobicity at position 16 in CA(1–8)-MA(1–12) by substituting Trp or Phe induced a significant increase in hemolytic activity without a considerable change in either antibacterial or antitumor activity. Therefore, these results suggested that the appropriate flexibility in the hinge region of CA-MA and CA-ME hybrid peptides and the appropriate hydrophobicity at position 16 in the hydrophobic region of CA (1–8)-MA(1–12) are important in potent antibacterial and antitumor activity with no hemolytic effect.     

Antimicrobial activity of 5-arylidene aromatic derivatives of hydantoin. Part 2

Various 5-chloroarylidene-2-amino substituted derivatives of imidazoline-4-one were synthesized and evaluated for their activity in vitro against Mycobacterium tuberculosis and other type strains of bacteria and fungi. 2-Chloro- and 2,4-dichlorobenzylidene substituted hydantoins exhibited antimycobacterial effect. The most potent compounds 3i, 3j, 3o, 3q and 3s were classified for further tests. The antimitotic effect of the investigated hydantoins was also examined.     

Antinociceptive,anti-inflammatory,and antioxidant properties of Phoradendron piperoides leaves

Phoradendron piperoides (Kunth) Trel. (Viscaceae) is a parasitic plant widely distributed in regions of the Brazilian northeast. Different species of Phoradendron are used in folk medicine for the treatment of cough, influenza, gastrointestinal and female disorders, and pain. In order to evaluate the actions of this plant, studies were performed on antinociceptive, anti-inflammatory, and antioxidant activities. The methanol extract (ME) and dichloromethane, ethyl acetate, and methanol partitions of P. piperoides leaves were used in the following experiments. Oral treatment with the ME elicited inhibitory activity (p?<?0.01) on the acetic acid effect at 100 (32.08%), 200 (34.46%), and 400?mg/kg (49.50%). P. piperoides ME reduced the formalin effect at the second phase (200 and 400?mg/kg, p?<?0.05); however, the ME did not elicit any inhibitory effect on the hot-plate test. Edema formation induced by carrageenan was reduced (p?<?0.05) with the ME by 28% (200?mg/kg) and 33% (400?mg/kg). ME, dichloromethane, ethyl acetate, and methanol partitions reacted with the DPPH radical and reduced the DPPH radical by 94.5, 37.2, 77.2, and 95.7%, respectively. ME, ethyl acetate, and methanol partitions exhibited low IC₅₀ values.     

Anti-inflammatory,Antinociceptive, and Neuropharmacological Activities of Clerodendron viscosum.

Abstract

The crude methanol extract of Clerodendron viscosum. Vent. (Verbenaceae) leaves was evaluated for its anti-inflammatory, antinociceptive, and neuropharmacological activities. When given orally to rats at doses of 200 and 400 mg/kg of body weight, the extract showed a significant (p < 0.001) anti-inflammatory activity against carrageenan-induced rat paw edema comparable with the standard drug phenylbutazone at the dose of 100 mg/kg of body weight. It also produced a significant writhing inhibition in acetic acid–induced writhing in mice at the oral dose of 250 and 500 mg/kg of body weight (p < 0.001), which was comparable with the standard drug diclofenac sodium at the dose of 25 mg/kg of body weight. Moreover, when given intraperitoneally to albino mice, it potentiated the pentobarbital-induced sleeping time (p < 0.001), decreased the open field score in open field test (p < 0.001), decreased the number of holes crossed from one chamber to the other in the hole-cross test (p < 0.001), and decreased the head dip responses in the hole-board test (p < 0.001) at the dose of 250 and 500 mg/kg of body weight. The overall results tend to suggest the anti-inflammatory, antinociceptive, and central nervous system depressant activities of the crude methanol extract of Clerodendron viscosum..     

Hemorrhagic activity of the Duvernoy''s gland secretion of the xenodontine colubrid Philodryas patagoniensis from the north-east region of Argentina

Colubrid snakes belonging to Philodryas genus, widespread all over South America, bring about lesions (swelling, ecchymosis, transient bleeding from the bite site punctures), that are similar to those produced by Bothrops species (yarará). In the present work we began the characterization of Philodryas patagoniensis venom. We examined if this venom produces hemorrhagic lesions as those observed in victims bitten by Philodryas olfersii. Hemorrhagic, proteolytic and fibrinogenolytic activities were evaluated, and histological observations in samples of gastrocnemius muscle were carried out. Inhibition studies were carried out in metal chelator (ethylenediaminetetraacetic acid) presence. Our results show a small Minimum Hemorrhagic Dose (MHD=0.035 μg) and a high proteolytic activity (143 U/mg), and prove the capacity of this venom to degrade fibrinogen in vitro rendering it unclottable by thrombin, supporting the presence of proteases, principally metalloproteases, in P. patagoniensis venom that are able to alterate the vascular wall and degrade fibrinogen, being both activities responsible of a high hemorrhagic activity.     

New thiazolyl-pyrazoline derivatives bearing nitrogen mustard as potential antimicrobial and antiprotozoal agents

A new series of N-substituted pyrazoline derivatives 6a–g , 7a–g , 8a–g , and 9a–g was synthetized by reaction of hydrazine derivatives and chalcone–thiazole hybrids bearing nitrogen mustard 5a–g . The chalcones 5a–g were obtained by Claisen–Schmidt condensation of thiazole-2-nitrogen mustard 3 and selected acetophenones 4a–g . These new compounds 6/7/8/9a–g were screened for their antifungal activity against Cryptococcus neoformans, with IC₅₀ values of 3.9–7.8 µg/ml for the N-3,5-dichlorophenyl pyrazolines 9e – g . Interestingly, those compounds show low cytotoxic effects toward erythrocytes (RBC). In addition, N-acetyl ( 6a,b ) and N-formyl pyrazolines ( 7a , 7b , 7c , and 7g ) showed inhibitory activity against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, and vancomycin-intermediate S. aureus, with the most important minimum inhibitory concentration values ranging from 31.25 to 125 µg/ml. Regarding the antiprotozoal activity, thiazolyl-pyrazolines 9g , 8f , and 7c display high activity against Plasmodium falciparum, Leishmania (V) panamensis, and Trypanosoma cruzi, with EC₅₀ values of 11.80, 6.46, and 4.98 μM, respectively, and with 7c being approximately 2.6-fold more potent than benznidazole with a selectivity index of 1.61 on U-937 human cells, showing promising potential as a novel antitrypanosomal agent.