合成的类脂A亚单位类似物及其与胞壁酰二肽衍生物结合物的佐剂活性

脂多糖(LPS)是革兰阴性菌的内毒素,位于菌体表面,类脂是LPS的有效成份,它的化学结构已经确定.Shiba等化学方法合成了类脂A.合成的大肠杆菌类脂A(化合物506)的内毒素活性基本与LPS相同,但它的亚单位类似物(即GLA化合物)的致病毒性和热原性很低,大约只有天然类脂A或合成类脂A的1/50～1/10000,却具有有效的免疫学活性.在GLA化合物中(GLA-27、GLA-59和GLA-60),与GLA-27和GLA-     

几种天然来源的细胞毒化合物

本文介绍了几种来源于植物和海洋生物的细胞毒化合物的研究概况。这些被分离并经结构鉴定的化合物均具有较强的细胞毒活性，其中一些是新发现的化合物。     

国内首次合成新型甘露碳糖苷

华东理工大学陈国荣教授等与法国罗纳阿尔卑斯大区科研人员合作，在国内首次合成了不饱和甘露碳糖苷，该成果日前已通过上海市科委主持的鉴定。专家认为，该成果对天然产物糖类似物创新药物研究具有重要价值。研究人员在国内外首次合成醌类及烯丙基类15个新型碳糖苷化合物。根据国家新药筛选中心的生物活性测试结果，发现其中烯丙基类碳糖苷化合物具有良好的体外免疫调节作用。     

褐藻某些化学组分研究新进展

从褐藻中分离出许多化学结构新颖的新化合物，一些具有独特的生物活性。本文按萜类，类脂，甾醇，酚类，其他化合物等化学结构类型概述了1993－2000年间报道的新的褐藻化学成分。     

海洋甾体化合物的研究进展

海洋来源的甾体化合物结构新颖，许多具有独特的生物活性。本文按海洋生物的门类综述了1996年－2000年间报道的新的海洋甾体化合物。     

海洋萜类化合物及其生物活性研究进展

综述海洋生物萜类化合物的结构特征、生物来源、生物活性及应用等,以期为海洋生物萜类的深入研究及开发提供参考。     

三萜糖苷的避孕活性——海参毒素A_1+B_1和海参素A的实验研究

已知有些植物的三萜糖苷有避孕作用。作者从海洋生物刺参(Stichopus japonicus)熬煮废液中分离出含三萜糖苷的海参毒素(holoto-xin)A_1和B_1,两者结构的唯一不同是海参毒素A_1在R(?)位上多一个CH_3。又从热带海参     

岗松枝叶正丁醇萃取部位的化学成分

从岗松（Baeckea frutescens L.）枝叶正丁醇萃取部位分离鉴定了12个化合物，分别为：槲皮素（1），杨梅素（2），槲皮素3-O-α-L-吡喃鼠李糖苷（3），杨梅素3-O-α-L-吡喃鼠李糖苷（4），槲皮素3-O-α-L-呋喃阿拉伯糖苷（5），槲皮素3-O-β-D-吡喃木糖苷（6），槲皮素3-O-α-L-吡喃阿拉伯糖（7），槲皮素4′-O-β-D-吡喃葡萄糖苷（8），山柰酚 3-O-α-L-呋喃阿拉伯糖苷（9），山柰酚3-O-α-L-吡喃鼠李糖苷（10），myricetin 3-O-（2′′-O-galloyl）-α-L-rhamnopyranoside（11），myricetin 3-O-（3′′-O-galloyl）-α-L-rhamnopyranoside（12）。其中化合物5~12为首次从该植物枝叶中分离得到。     

类脂囊泡在不同给药途径中的研究进展

纳米载体具有靶向递送药物至特定部位的潜力,因此纳米载体的开发一直受到广泛关注。近10年里,制备基于表面活性剂的纳米囊泡以改善药物递送,引起了研究者们的兴趣。类脂囊泡由非离子表面活性剂在水性介质中自组装形成,具有既能包裹亲水性化合物又能包裹亲脂性化合物的囊泡结构,广泛应用于各种给药途径。与脂质体相比,类脂囊泡不仅具有与其相似的优点,如既能装载亲水性药物又能装载亲脂性药物,而且类脂囊泡的制备方法更简单,制备原料价格更便宜,稳定性更好,克服了脂质体的主要缺点。本文综述了类脂囊泡各制备方法的优缺点及其在不同给药途径中的研究进展。     

抗生素糖基转移酶研究进展

糖苷类抗生素是临床上广泛应用的抗菌和抗肿瘤化合物。该类化合物在体内由糖基转移酶催化，糖基化反应通常在抗生素生物合成的最后发生，糖基的位置、类型和数量对糖苷类抗生素的活性有很大的影响。本文综述了糖基转移酶的种类、功能、特性及其在组合生物合成中的应用与研究前景。     

Structure and biological activity of glycosphingolipids from starfish and feather stars

Glycosphingolipids (GSLs) are contained in a various cell membranes and have recently been implicated in many physiologic functions. They are classified based on their sugar moieties into ceramides, cerebrosides, sulfatides, ceramide-oligohexosides, globosides, and gangliosides. A number of GSLs have been obtained from marine invertebrates such as echinoderms, poriferans, and mollusks and have unique biological activities. During the course of our search for biologically active GSLs from echinoderms, we conducted the isolation and structural elucidation of GSLs from starfish and feather stars and found numerous GSLs, some of which have unique structures. In particular, gangliosides from feather stars were unique in that the sialic acids bind to inositol-phosphoceramide. We also found that the GSLs from starfish and feather stars possess neuritogenic activity toward the rat pheochromocytoma cell line PC12, antihyperglycemic effects against type 2 diabetic BKS. Cg-m+/+Leprdb/J (db/db) mice, and antiosteoporosis effects toward the osteoporosis model mice (OVX mice). These biological activities are thought to be related to dementia, osteoporosis, and diabetes, which are becoming social problems, and are expected to become the seeds of preventive or therapeutic drugs for these illness.     

Chemo-pharmaceutical studies on the glycosphingolipid constituents from echinoderm,sea cucumbers,as the medicinal materials

Glycosphingolipids (GSLs), together with glycopeptides, are typical constitutents of various cell membranes in a wide variety of organisms. In particular, it is known that GSLs have numerous physiological functions due to variations in the sugar chain, in spite of the very small quantity of constituents. Those are classified into cerebrosides, sulfatides, ceramide oligohexosides, globosides, and gangliosides based on the constituent sugars. Gangliosides, sialic acid-containing GSLs, are especially enriched in the brain and nervous tissues and are involved in the regulation of many cellular events. Recently, a number of GSLs have been isolated from marine invertebrates such as echinoderms, poriferans, and mollusks. We have also been researching biologically active GSLs from echinoderms to elucidate the structure-function relationships of GSLs and to develop novel medicinal resources. This review summarizes the structures and biological activities of GSLs from sea cucumbers. This study showed that the characteristics of GSLs and structure-activity relationships had neuritogenic activity toward the rat pheochromocytoma cell line PC12. That is, most of the cerebroside constituents of the sea cucumber are same glucocerebrosides as in other animals, except for some constituents, while the ganglioside constituents were unique in that a sialic acid directly binds to the glucose of cerebroside, they are mutually connected in tandem, and some are located in the internal parts of the sugar chain. It also became apparent that sialic acid is indispensable for the neuritogenic activities.     

Chemotherapy by slowing glucosphingolipid synthesis

The hypothesis offered here is that many different illnesses could be treated by slowing the synthesis of glucosphingolipids (GSLs) with a suitable inhibitor. In people with inadequate hydrolases for the GSLs (e.g. Gaucher's disease), the lipids accumulate to a pathological degree. It should be possible to eliminate the accumulation by slowing the synthesis of the GSLs to match the ability of the patient to degrade them. In people with cancer, the tumors secrete excessive amounts of GSLs, which block the ability of the immune system to attack the tumor cells. By blocking the synthesis of tumor GSLs, it should be possible to enable the patient to generate antibodies and activated T cells that can destroy the tumor. Tumors exhibiting multidrug resistance may do so by synthesizing GSLs even faster than usual. It should be possible to restore the sensitivity of the tumor to anti-cancer drugs by inhibiting their synthesis of GSLs. Metastasis of tumors also appears to require the formation of GSLs, so an inhibitor should help block tumor dissemination. Diabetics tend to have high levels of blood glucose, which acts to stimulate kidney growth via more rapid synthesis of GSLs. This pathological growth can be blocked by inhibiting the formation of kidney GSLs. Viruses, bacteria, and bacterial toxins have been found to bind to specific GSLs of human and animal cells. Presumably, this binding leads to the damaging process of infection. It should be possible to treat such infections by depleting the host's body of its GSLs.     

Synthesis and biological evaluation of antifungal activities of novel 1,2-trans glycosphingolipids

The synthesis and in-vitro biological evaluation of antifungal activities of a series of 1,2-trans glycosphingolipids (GSL) against Candida albicans, Candida parapsilosis, and Candida tropicalis were described. The preliminary study indicated that the sort of sugar moiety of GSLs affected their antifungal activities and selectivities towards the three Candida species, and the permeability might not be the sole parameter affecting their antifungal properties as presumed before, which would bring new clues to understand the antifungal profile for these types of compounds.     

Good Samaritan laws and overdose mortality in the United States in the fentanyl era

BackgroundAs of July 2018, 45 United States (US) states and the District of Columbia have enacted an overdose Good Samaritan law (GSL). These laws, which provide limited criminal immunity to individuals who request assistance during an overdose, may be of importance in the current wave of the overdose epidemic, which is driven primarily by illicit opioids including heroin and fentanyl. There are substantial differences in the structures of states’ GSL laws which may impact their effectiveness. This study compared GSLs which have legal provisions protecting from arrest and laws which have more limited protections.MethodsUsing national county-level overdose mortality data from 3109 US counties, we examined the association of enactment of GSLs with protection from arrest and GSLs with more limited protections with subsequent overdose mortality between 2013 and 2018. Since GSLs are often enacted in conjunction with Naloxone Access Laws (NAL), we examined the effect of GSLs separately and in conjunction with NAL. We conducted these analyses using hierarchical Bayesian spatiotemporal Poisson models.ResultsGSLs with protections against arrest enactment in conjunction with a NAL were associated with 7% lower rates of all overdose deaths (rate ratio (RR): 0.93% Credible Interval (CI): 0.89–0.97), 10% lower rates in opioid overdose deaths (RR: 0.90; CI: 0.85–0.95) and 11% lower rates of heroin/synthetic overdose mortality (RR: 0.89; CI: 0.82–0.96) two years after enactment, compared to rates in states without these laws. Significant reductions in overdose mortality were not seen for GSLs with protections for charge or prosecution.ConclusionGSLs with more expansive legal protections combined with a NAL, were associated with lower rates of overdose deaths, although these risk reductions take time to manifest. Policy makers should consider enacting and implementing more expansive GSLs with arrest protections to increase the likelihood people will contact emergency services in the event of an overdose.     

The effectiveness of drug-related Good Samaritan laws: A review of the literature

BackgroundThe United States (US) and Canada are in the midst of an opioid overdose epidemic. Many people who use illicit drugs (PWUD) do not call an emergency number 911 at the scene of an overdose due to fear of arrest. In the US and Canada, when an individual calls 911, both emergency medical services (EMS) and police are notified to attend the overdose event. In response, many settings in North America have introduced drug-related ‘Good Samaritan’ laws (GSLs) that aim to encourage PWUD to call 911 by providing legal immunity (mainly protections from drugs possessed for personal use) to those at the scene of the overdose. However, little is known about the effectiveness of these laws in increasing calls to 911.MethodsWe conducted a literature review of the published literature between 2005 and 2019 to examine the effectiveness of GSLs. Searches were referenced using keywords that included: “good samaritan”, “overdose”, “emergency services”, and “drug use”.ResultsAmong 68 articles identified, after eligibility screening, 12 publications were deemed to meet the inclusion criteria. These publications were largely quantitative observational studies (9/12), with a minority (3/12) being qualitative in design. Two major themes emerged: “knowledge of GSLs and calling EMS” and “overdose-related hospital admissions and mortality assessment”.ConclusionAt this time, the current body of evidence regarding the effectiveness of GSLs in increasing calls to EMS and reducing drug-related harms is limited and mixed. Studies show that PWUD have low levels of knowledge regarding GSLs while some evidence suggests their effectiveness in increasing calls to EMS at the scene of an overdose. Given the current overdose crisis, further investigation is warranted to establish the effectiveness of these laws in reducing drug-related harms.     

6个小分子海洋药物的全合成方法

骨架新颖、活性独特的海洋天然产物是药物先导化合物的重要来源,但由于海洋样品采集困难、一些高活性天然产物在海洋生物体中含量低微,往往难以获取足够量的化合物进行后续药物的深入研究,成为海洋小分子药物研究的瓶颈之一。现代有机合成尤其是海洋天然产物全合成的迅猛发展,为获取复杂小分子海洋活性天然产物提供了一个重要手段。探究复杂小分子海洋天然产物合成的新策略和新方法,建立高效、高选择性的规模化制备技术,是国际海洋药物研究的热点。本文就6个上市的小分子海洋药物的全合成研究作一概述,重点阐述有机合成对于成药分子规模化制备的途径。     

Liposomal formulation of glycosphingolipids from Sphingomonas paucimobilis induces antitumour immunity in mice

Natural Killer T (NKT) cells play an important role in host’s anti-tumour immune response. Glycosphingolipids (GSLs) isolated from Sphingomonas paucimobilis have the ability to stimulate NKT cells. In this study, the activity of free GSLs or GSLs-incorporated liposomes (glycosphingosomes) was investigated against dimethyl-α-benzanthracene (DMBA)-induced tumours in mice. The anti-tumour immunity of GSLs- or glycosphingosomes-loaded bone marrow-derived dendritic cells (BMDCs) was investigated in tumour-bearing mice. The Immunotherapeutic potential of co-administration of liposomal doxorubicin (Lip-Dox) and GSLs or glycosphingosomes was assessed by measuring cytokine levels and VEGF in the tumour tissues. Pretreatment with glycosphingosomes significantly delayed the frequency of tumour formation. Immunotherapy with glycosphingosomes-loaded BMDCs increased serum IFN-γ level and survival rate in mice. The effect of immunotherapy was dependent on effector functions of NK cells because the depletion of NK cells abolished the effects of immunotherapy. There was reduced tumour growth with low expression of VEGF in the group of mice treated with glycosphingosomes and Lip-Dox combination. Moreover, the splenocytes secreted higher levels of IFN-γ, IL-12 and lower TGF-β level. The results of this study indicate that glycosphingosomes can induce better antitumour immunity and may be considered a novel formulation in antitumour therapy.     

具有抗菌活性的海洋真菌天然产物研究新进展

近年来,病原微生物的耐药性已严重威胁到人类健康,从海洋微生物中寻找对耐药菌敏感的化合物成为研究的热点,其中海洋真菌因其能够产生大量结构新颖、活性显著的代谢产物而受到广泛关注。本文按照海洋真菌的来源进行分类,从海洋动物来源真菌、红树林来源真菌、海藻来源真菌、海水来源真菌等4个方面,综述了2014年来发表的具有抗菌活性的海洋真菌来源的新的天然产物,主要介绍天然产物的化学结构和生物活性,化合物结构式曾有文献报道的未包括在内,为具有抗菌活性的海洋真菌天然产物的进一步研究开发提供了参考。     

海洋生物中抗氧化活性成分的研究进展

近30年来，从海洋生物中分离到许多具有抗氧化活性的物质，本文按这些抗氧化活性物质的种类。综述了来自海洋生物的抗氧化活性物质的研究进展。