微生物来源酸性鞘磷脂酶抑制剂NF-0265A的研究

 目的筛选信号转导相关疾病中重要靶点-酸性鞘磷脂酶抑制剂。方法使用ODS柱色谱,制备TLC和SephadexLH-20色谱等方法进行化合物的分离纯化,利用紫外、质谱等理化分析以及核磁共振等分析方法进行结构解析,利用酸性和中性SMase的活性测定方法进行活性评价。结果从微生物代谢产物的菌种中,筛选得到一个活性化合物NF-0265A,其对酸性SMase的IC₅₀为68.7μmol·L^-1。对中性SMase的活性测定的结果表明,此物质在200μmol·L^-1的浓度下未见抑制作用,此化合物的化学结构与TAN-1446A的甲醇加成物相同。结论NF-0265A为第一个微生物来源的酸性SMase特异性的抑制剂,该化合物在信号转导系统和免疫系统的活性尚未见报道。     

微生物来源的卡斯帕酶-3抑制剂F03ZA-673A的研究

 目的筛选细胞凋亡相关疾病中重要靶点——卡斯帕酶-3抑制剂。方法利用自建的快速、高效、高通量的卡斯帕酶-3抑制剂的筛选方法,从数千株菌株中筛选阳性菌株。阳性菌株的发酵产物进行分离纯化获得活性化合物,再通过对活性化合物的紫外、质谱、核磁等理化数据的分析进行结构鉴定。结果筛选得到一个活性化合物F03ZA-673A。该化合物对卡斯帕酶-3有较强的抑制活性,IC₅₀=21.1μmol·L^-1,它与L-671,776结构相同。结论F03ZA-673 A为一个活性较强的微生物来源卡斯帕酶-3特异性的抑制剂,该化合物对卡斯帕酶-3的抑制活性未见国内外报道。     

天然来源的人类免疫缺陷病毒1整合酶抑制剂

 目的简要介绍天然来源的人类免疫缺陷病毒1(HIV-1)整合酶抑制剂以及几个研究热点化合物的性质、特点和构效关系。方法以国内外的研究为依据,对HIV-1整合酶的天然抑制剂进行分类综述,简要介绍几个研究热点化合物的性质、特点和构效关系。结果与结论根据化学结构,将HIV-1整合酶的天然抑制剂分为酮类、酚类、生物碱类、萜类以及蛋白和多肽类。以天然抑制剂及现有合成药物的结构特征和活性为指导,通过化学改造,有望获得更有效乃至选择性更强的HIV-1整合酶抑制剂。     

HIV-1整合酶抑制剂的研究进展

 目的 介绍HIV治疗的新靶点——整合酶抑制剂,为寻找新的有效的抗艾滋病药物提供理论依据。方法 根据近年来国外文献进行综述。结果与结论 HIV复制过程中还有另一个重要的酶——整合酶,使病毒基因组整合于宿主细胞染色体,病毒在体内长期潜伏。整合酶是HIV自身特有的酶,也是一个抗HIV药物设计的理想靶点。目前整合酶抑制剂有DNA结合剂和拓扑异构酶抑制剂;核苷类;肽类;多羟基化芳香族化合物四大类。     

麝香糖蛋白成分对大鼠中性白细胞花生四烯酸代谢酶的作用

采用体外温孵系统,观察麝香糖蛋白成分麝香-1对大鼠中性白细胞花生四烯酸代谢酶,包括磷脂酶A2、5-脂氧酶和环氧酶活性的影响。结果表明:终浓度为1～100μg/ml的麝香-1使AA释放量增加6.0%～21.6%,使LTB4生成量减少9%～81%,使6-酮-PGF1α生成量增加18.2%～85.4%。     

天然产物中脂肪酸合酶抑制剂的筛选

近年来研究表明,脂肪酸合酶已成为治疗癌症与肥胖的一个好的新靶点,具有重要的研究意义。目前发现的FAS抑制剂很少,仅浅蓝菌、C75等,且都具有不稳定、毒性高等缺点。本文通过超声提取法对40种天然产物进行提取,然后把各自所得提取液进行酶抑制作用的研究,从中初步筛选出14种尚未发现的具有抑制FAS生物活性的药物,其中13种药物高度抑制FAS活性,为寻找无毒、低成本的FAS抑制剂以解决肥胖问题提供依据。     

一种新的血浆中磺胺二甲嘧啶及其代谢物的测定方法及在N-乙酰化分型中应用

目的：测定血浆中磺胺二甲嘧啶及其代谢物，研究其在体内乙酰化表型。方法：用乙腈直接沉淀血浆蛋白，处理后样品在流动相为乙腈水醋酸（１６．５∶８３．５∶０．０５），流速１．０ｍｌ·ｍｉｎ－１，紫外测定波长２６０ｎｍ条件下进样。结果：磺胺二甲嘧啶和乙酰磺胺二甲嘧啶相关性分别为０．９９９９和０．９９９６。方法的平均回收率为（９９．４９±３．６２）％和（９９．８９±０．８７）％。１２０名健康志愿者服用磺胺二甲嘧啶片后，用本方法测定体内药物浓度，得快乙酰化者与慢乙酰化者之比为１０１∶１９。结论：方法简单、快速、灵敏，能较好地Ｎ乙酰化酶表型。     

一种新的血浆中磺胺二甲嘧啶及其代谢物的测定方法及在N-乙酰化分型中应用

 目的:测定血浆中磺胺二甲嘧啶及其代谢物，研究其在体内乙酰化表型。方法:用乙腈直接沉沈血浆蛋白，处理后样品在流动相为乙腈-水-醋酸(16.5:83.5:0.05)，流速1.0 ml·min^-1,紫外测定波长260 nm条件下进样。结果:磺胺二甲嘧啶和乙酰磺胺二甲嘧啶相关性分别为0. 999 9和0. 999 6。方法的平均回收率为(99. 49±3.62)%和(99.89±0.87)%。 120名健康志愿者服用磺胺二甲嘧啶片后，用本方法测定体内药物浓度，得快乙酰化者与慢乙酰化者之比为101:19。结论:方法简单、快速、灵敏，能较好地N-乙酰化酶表型。     

微生物来源的抗耐药菌活性化合物SIPI-1140A和SIPI-1140B的研究

目的：分离链霉菌SIPT—1140菌株生物合成具有抑制耐药菌活性的化合物。方法：优化发酵条件，进行放大发酵；发酵液经离心、乙酸乙酯萃取、硅胶柱层析等方法，从发酵液中分离出化合物SIPI-1413lA和SIPI-1140B，并测定化合物的数据图谱和生物学活性结果：通过其理化性质、质谱、紫外、红外和核磁共振等图谱数据的分析，确定化合物SIPI—1140A和B的化学结构；生物学活性研究发现两个化合物具有强的抑制甲氧西林耐药的金黄色葡萄菌活性结论：链霉菌SIPI-1140产生的两个活性化合物SIPI—1140A和B均属于酯肽类抗生素，分别与文献报道的Quinomcyn A (Echinomycin)和Quimohycin C结构一致.     

清肠栓对溃疡性结肠炎急性期大鼠结肠黏膜中性粒细胞浸润的影响

目的从中性粒细胞浸润的角度,探讨中药清肠栓治疗溃疡性结肠炎(UC)急性期的作用机理。方法 SD大鼠48只,分为正常组、模型组、清肠栓组和柳氮磺胺吡啶(SASP)组,每组各12只。用三硝基苯磺酸(TNBS)诱导大鼠UC急性期模型。造模后第3日开始给药,连续给药7d后处死。记录病变结肠组织损伤指数;组织病理学观察结肠黏膜病理变化及中性粒细胞浸润情况;Elisa检测血清及结肠组织中的髓过氧化物酶(MPO)、中性粒细胞弹性蛋白酶(NE)含量。结果动物模型病理观察有大量炎症细胞浸润(以中性粒细胞和淋巴细胞为主);清肠栓组及SASP组可见组织修复征象;血清中MPO含量各组差异无统计学意义;血清中NE含量正常组与模型组差异无统计学意义;组织上清中MPO及NE模型组较正常组明显增高,清肠栓组和SASP组较模型组降低。结论清肠栓对大鼠TNBS诱导的急性UC模型有治疗作用,能够减轻UC急性期结肠黏膜大量中性粒细胞浸润的状态,促进组织修复,并通过调节MPO、NE的蛋白表达,减少这两种物质对组织的损伤。     

Scoparic acid A, a beta-glucuronidase inhibitor from Scoparia dulcis.

The 70% EtOH extract of Scoparia dulcis showed inhibitory activity against beta-glucuronidase from bovine liver. Bioassay-directed fractionation of the active extract led to the isolation of three labdane-type diterpene acids, scoparic acid A [1] [6-benzoyl-12-hydroxy-labda-8(17), 13-dien-18-oic acid], scoparic acid B [2] [6-benzoyl-14,15-dinor-13-oxo-8(17)-labden-18-oic acid], and scoparic acid C [3] [6-benzoyl-15-nor-14-oxo-8(17)-labden-18-oic acid], the structures of which were established by spectral means, including X-ray analysis. Scoparic acid A was found to be a potent beta-glucuronidase inhibitor.     

Penasulfate A, a new alpha-glucosidase inhibitor from a marine sponge Penares sp

A new alpha-glucosidase inhibitor, penasulfate A, has been isolated from a marine sponge Penares sp.(1) Its structure was elucidated by spectral and chemical methods to be a scalemic mixture of methyl pipecolates acylated with a novel sulfated fatty acid.     

Isolation of a novel tyrosine kinase inhibitor, lavendustin A, from Streptomyces griseolavendus

A potent tyrosine kinase inhibitor, lavendustin A [1], has been isolated from a butyl acetate extract of Streptomyces griseolavendus culture filtrate. It inhibits epidermal growth factor receptor-associated tyrosine kinase with an IC50 of 4.4 ng/ml, which is about 50 times more inhibitory than erbstatin. It does not inhibit protein kinase A or C. Its structure, determined by spectral data and total synthesis, is novel, having a tertiary amine in the center with substituted benzyl and phenyl groups. Lavendustin A competes with ATP and is noncompetitive with the peptide. Its structure-activity relationship is discussed.     

Sculezonones A and B, two metabolites possessing a phenalenone skeleton from a marine-derived fungus Penicillium species

Two new metabolites possessing a phenalenone skeleton, sculezonones A (1) and B (2), were isolated from cultured broth of the fungus Penicillium sp., which was separated from the Okinawan marine bivalve Mytilus coruscus, and the structures were elucidated by spectroscopic data.     

Derivative Synthesis of Wanpeinine A, a Major Steroidal Alkaloid from Fritillaria shuchengensis

Objective To design and synthesize derivatives of wanpeinine A,the main steroidal alkaloid isolated from the plant Fritillaria shuchengensis,and further study on the structure-activity relationship of the steroidal alkaloid.Methods Acylation and alkylation were used to synthesize the derivatives and their structures were identified via NMR and MS.Results The acylation of wanpeinine A(1) produced 3β,6α-diacetylwanpeinine A(2),3β,6α-dipropionyl-wanpeinine A(3),3β,6α-dichloracetylwanpeinine A(4),3β,6α-dibenzoy...     

Pseudosemiglabrin, a platelet aggregation inhibitor from tephrosia semiglabra

Following bioassay-directed fractionation procedures, two 7-oxygenated-8-prenylflavones, (-)-pseudosemiglabrin [1] and (-)-semiglabrin [2], were isolated from an MeOH extract of Tephrosia semiglabra. (-)-Pseudosemiglabrin [1] displayed in vitro inhibitory effects on human platelet aggregation.     

Biological activities of the secondary metabolites isolated from Zieria smithii and Zanthoxylum elephantiasis on microorganisms and brine shrimps

Eight secondary metabolites, two isolated from Zieria smithii and six from Zanthoxylum elephantiasis were investigated for their biological (antimicrobial and cytotoxic) activities against 15 pathogenic microorganisms and on brine shrimps. Canthine-6-one obtained from Z. elephantiasis was shown to have significant antibacterial, antifungal and cytotoxic activities. 6-Methoxydihydrochelerythrine also from the Z. elephantiasis showed satisfactory antibacterial properties but no effect on brine shrimps. Dipetalolactone, methyl eugenol and 3,4-dimethoxycinnamaldehyde were found to have antibacterial activities against a single pathogenic strain. © 1997 John Wiley & Sons, Ltd.     

Panepophenanthrin,from a mushroom strain,a novel inhibitor of the ubiquitin-activating enzyme

Screening for inhibitors of the ubiquitin-proteasome pathway, considered to regulate important cellular events and linked to serious diseases as well, led to isolation of a new compound, panepophenanthrin, from the fermented broth of a mushroom strain, Panus rudis Fr. IFO 8994. This is the first inhibitor of the ubiquitin-activating enzyme, which is indispensable for the ubiquitin-proteasome pathway. The structure of panepophenanthrin was determined by NMR and X-ray crystallographic analyses as 1,3a,10-trihydroxy-10c-(3-hydroxy-3-methylbut-1-enyl)-5,5-dimethyl-1,2,3,3a,5,5a,8,9,10,10a,10b,10c-dodecahydro-4-oxa-2,3,8,9-diepoxyacephenanthrylen-7-one.     

Lehualides A-D, metabolites from a Hawaiian sponge of the genus Plakortis

A collection of an undescribed marine sponge of the genus Plakortis yielded four new "polyketide-derived" metabolites, lehualides A-D (1-4). The structures of compounds 1-4 were elucidated by interpretation of spectral data. Compound 2 demonstrated cytotoxicity against an ovarian cancer cell line, while compound 4 was active against both ovarian cancer and leukemia cell lines.