N－甲基－N－（α－取代萘甲基）取代苄胺类化合物的合成及抗真菌活性

报道２５个Ｎ－甲基－Ｎ－（α－取代萘甲基）取代苄胺类化合物的合成及抗真菌活性。抑菌测试结果表明，目标化合物对于８种试验菌种均有不同程度的抑菌活性，化合物６，７，８，１０，１１和２１等活性为ｎａｆｔｉｆｉｎｅ的４～２０倍，化合物８，１０，１１和２１等活性为ｂｕｔｅｎａｆｉｎｅ的２～１０倍，化合物８，９，１０，１１和２１等对Ｓｐｏｒｏｔｒｉｃｈｕｍｓｃｈｅｎｃｋｉｉ及Ａｓｐｅｒｇｉｌｌｕｓｆｕｍｉｇａｔｕｓ的活性为ｃｌｏｔｒｉｍａｚｏｌｅ的８～１５倍，化合物７，８，９和２１等对Ｃｒｙｐｔｏｃｃｏｃｕｓｎｅｏｆｏｒｍａｎｓ亦表现出较高活性，ＭＩＣ为０．３１～１．２５μｇ·ｍｌ－１。     

1－［2－（取代苯基）烯丙基］－1H－唑类抗真菌化合物的合成

根据唑类抗真菌药物的构效关系，合成了１４个１－［２－（取代苯基］烯丙基］－１Ｈ－唑类化合物。体外抗真菌活性试验结果表明，此类化合物对几种常见的深部致病真菌都有不同程度的抗真菌活性。     

2，4－二氨基5－氟－6－取代苄氨基喹唑啉的合成及生物活性

本文报道２，４－二氨基－５－氟－６－取代苄氨基喹唑啉类化合物的合成及抗疟、抗肿瘤和抗菌活性，这类化合物的合成是由５－氟－２，４，６－三氨基喹唑啉（６ａ）与取代苯甲醛缩合成Ｓｃｈｉｆｆ碱，然后经还原、甲酰化、亚硝化或甲基化制得。５－氟－２，４，６－三氨基喹唑啉（６ａ）尚未见文献报道，由５－氟－２，４－二氨基喹唑啉（４）经硝化生成异构体５ａ和５ｂ分离得５ａ后再经还原制得。经对伯氏鼠疟原虫Ｐｌａｓｍｏｄｉｕｍｂｅｒｇｈｅｉ抑制性治疗筛选，有６个化合物Ｉ２，４．５，６和ＩＩ５，６以每日１ｍｇ·ｋｇ－１，给药４天，抑制率为１００％；体外抗肿瘤活性以Ｉ４最强，对Ｌ１２１０白血病细胞的ＩＣ５０为９．８６×１０－４μｇ·ｍｌ－１，优于氨甲蝶呤（ＭＴＸ）；经对１８种常见菌进行体外筛选，发现对肺炎双球菌Ｄｉｐｌｏｃｏｃｃｕｓｐｎｅｕｍｏｎｉａｅ活性较好。     

3－酮－地索高诺酮在家兔体内的药物动力学

以高效液相色谱分析法测定按２ｍｇ·ｋｇ－１剂量给家兔皮下注射３－酮－地索高诺酮后０．２５～２４ｈ的血药浓度，其血药浓度－时间曲线符合二室开放模型，药物动力学方程为Ｃ＝２５７．０７ｅ－０．７１ｔ＋４２．２３ｅ－０．０５ｔ－２９９．３０ｅ－０．９３ｔ主要药物动力学参数：Ｔｋａ０．７８±０．１７ｈ，Ｔα１．２０±０．３０ｈ，Ｔβ１２．０９±４．１８ｈ，ＡＵＣ１３１２．９０±３８７．４５μｇ·ｈ￣（－１）·Ｌ￣（－１），Ｔ＿（ｍａｘ）１．６９±０．３９ｈ，Ｃ（ｍａｘ）＝１２８．２１±５０·７１μｇ·Ｌ￣（－１），Ｖ／Ｆ９．５０±４．３９Ｌ·ｋｇ（－１）。采用平衡透析法测得３－酮－地索高诺酮与兔血浆蛋白的结合率在８１．０９％～８４．６０％之间。     

强啡肽A－（1－13）类似物的合成及生物活性

用固相多肽合成方法，合成了强啡肽Ａ－（１－１３）（Ｉ）及其类似物［Ａｌａ８，Ｄ－Ｐｒｏ１０］－ＤＹＮＡ－（１－１３）－ＮＨ２（ＩＩ）和［Ｄ－Ａｌａ２，Ａｌａ８，Ｄ－Ｐｒｏ１０］－ＤＹＮＡ－（１－１３）－ＮＨ２（ＩＩＩ），并对其进行了镇痛活性试验和ＭＶＤ及ＲＶＤ试验。结果表明，合成产物均有镇痛活性，其中类似物ＩＩＩ的镇痛活性是１的３．６倍，ＲＶＤ试验活性比１强１３５倍，比已知的ｋ－受体强激动剂Ｕ５００４８８强１１倍。     

N－（1－乙氧羰基－3－苯氨甲酰基丙基）甘氨酰甘氨酸衍生物的合成

报道４个Ｎ－（１－［１－乙氧羰基－３－（对甲）苯氨甲酰基］丙基甘氨酰｝－Ｎ－取代甘氨酸（ＸＩ１～４）和５个１－［１－乙（或甲）氧羰基－３－（对甲）苯氨甲酰基］丙基－４－取代－１，４－哌嗪－２，５－二酮（ＸＩＩ１～５）共９个估计有血管紧张素转化酶抑制活性化合物的合成和鉴定。所有这些化合物及９个相应的酯（Ｘ１～９）均未见文献报道。药理初试结果，化合物ＸＩＩ２，ＸＩＩ５，ＸＩ４和ＸＩＩ１均有较强降压活性。     

3－酮－地索高诺酮在家兔体内的药物动力学

以高效液相色谱分析法测定按２ｍｇ·ｋｇ－１剂量给家兔皮下注射３－酮－地索高诺酮后０．２５～２４ｈ的血药浓度，其血药浓度－时间曲线符合二室开放模型，药物动力学方程为Ｃ＝２５７．０７ｅ－０．７１ｔ＋４２．２３ｅ－０．０５ｔ－２９９．３０ｅ－０．９３ｔ主要药物动力学参数：Ｔｋａ０．７８±０．１７ｈ，Ｔα１．２０±０．３０ｈ，Ｔβ１２．０９±４．１８ｈ，ＡＵＣ１３１２．９０±３８７．４５μｇ·ｈ￣（－１）·Ｌ￣（－１），Ｔ＿（ｍａｘ）１．６９±０．３９ｈ，Ｃ（ｍａｘ）＝１２８．２１±５０·７１μｇ·Ｌ￣（－１），Ｖ／Ｆ９．５０±４．３９Ｌ·ｋｇ（－１）。采用平衡透析法测得３－酮－地索高诺酮与兔血浆蛋白的结合率在８１．０９％～８４．６０％之间。     

广东省内常见乙肝检测ELISA试剂的抽样调查

广东省临床检验中心组织广州市九间三级甲等医院的免疫检验专家，抽样调查了九个有生产批文的试剂厂家出品的乙肝检测ＥＬＩＳＡ试剂。结果显示：不同厂家试剂的灵敏度相差１－５个稀释度，精密性为１．２８～６６．３％；九厂家试剂的平均特异性为８９．４～１００％、敏感性为７５～９４％、符合率为８６．５～９５．９％；五种品名试剂的平均特异性ＨＢｓＡｇ９８．８％、抗－ＨＢｓ９７．０％、ＨＢｅＡｇ９９．１％、抗－ＨＢｅ９６．２％、抗－ＨＢｃ８６．５％、平均敏感性ＨＢｓＡｇ８５．５％、抗－ＨＢｓ７８．６％、ＨＢｅＡｇ９０％、抗－ＨＢｅ７０．２％、抗－ＨＢｃ９３．１％，平均符合率ＨＢｓＡｇ９０％、抗－ＨＢｓ８９．９％、ＨＢｅＡｇ９５．１％、抗－ＨＢｅ８６．１％、抗ＨＢｃ９０．６％。     

N—〔3—（1H—1,2,4—三嗪—1—基）—2—（2,4—二氟苯基）—2—羟基—丙基 …

设计合成了Ｎ－〔３－（１Ｈ－１，２，４－三唑－１－基）－２－（２，４－二氟苯基）－２－羟基－丙基〕－氨基乙酸及其９个衍生物，均为未见文献报道的新化合物，初步药理试验表明：部分化合物对浅部真菌有一定的活性，除卡氏枝孢霉菌外，对其它深部真菌活性较弱，其中化合物（５ｅ），（５ｈ）对某些真菌的体外活性较强，明显优于氟康唑，但稍弱于酮康唑。     

α1受体拮抗剂DDPH异位手性碳类似物的合成及降压活性

以苯酚及其类似物（Ⅲ）和２－氯丙酸为原料，经中间体２－取代苯氧丙酰胺（Ⅵ１～９），用Ｚｎ－Ｃｌ２－ＫＢＨ４－ＴＨＦ－Ｃ６Ｈ５ＣＨ３体系还原、再成盐得９个新的ＤＤＰＨ异位手性碳类似物（Ⅱ１～９）．目的物和酰胺中间体的结构均经元素分析、红外光谱、核磁共振谱和质谱确证．大部分目的物的急性降压试验表明都有不同程度的降压活性，其中（Ⅱ２）和（Ⅱ５）尤为明显．     

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.     

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.     

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..     

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.     

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.