Verrucosamide,a Cytotoxic 1,4-Thiazepane-Containing Thiodepsipeptide from a Marine-Derived Actinomycete

A new cytotoxic thiodepsipeptide, verrucosamide (1), was isolated along with the known, related cyclic peptide thiocoraline, from the extract of a marine-derived actinomycete, a Verrucosispora sp., our strain CNX-026. The new peptide, which is composed of two rare seven-membered 1,4-thiazepane rings, was elucidated by a combination of spectral methods and the absolute configuration was determined by a single X-ray diffraction study. Verrucosamide (1) showed moderate cytotoxicity and selectivity in the NCI 60 cell line bioassay. The most susceptible cell lines were MDA-MB-468 breast carcinoma with an LD₅₀ of 1.26 µM, and COLO 205 colon adenocarcinoma with an LD₅₀ of 1.4 µM. Also isolated along with verrucosamide were three small 3-hydroxy(alkoxy)-quinaldic acid derivatives that appear to be products of the same biosynthetic pathway.     

Kurilosides A1, A2, C1, D,E and F—Triterpene Glycosides from the Far Eastern Sea Cucumber Thyonidium (= Duasmodactyla) kurilensis (Levin): Structures with Unusual Non-Holostane Aglycones and Cytotoxicities

Six new monosulfated triterpene tetra-, penta- and hexaosides, namely, the kurilosides A₁ (1), A₂ (2), C₁ (3), D (4), E (5) and F (6), as well as the known earlier kuriloside A (7), having unusual non-holostane aglycones without lactone, have been isolated from the sea cucumber Thyonidium (= Duasmodactyla) kurilensis (Levin) (Cucumariidae, Dendrochirotida), collected in the Sea of Okhotsk near Onekotan Island from a depth of 100 m. Structures of the glycosides were established by 2D NMR spectroscopy and HR-ESI mass spectrometry. Kurilosides of the groups A and E contain carbohydrate moieties with a rare architecture (a pentasaccharide branched by C(4) Xyl1), differing from each other in the second monosaccharide residue (quinovose or glucose, correspondingly); kurilosides of the group C are characterized by a unique tetrasaccharide branched by a C(4) Xyl1 sugar chain; and kurilosides of the groups D and F are hexaosides differing from each other in the presence of an O-methyl group in the fourth (terminal) sugar unit. All these glycosides contain a sulfate group at C-6 of the glucose residue attached to C-4 Xyl1 and the non-holostane aglycones have a 9(11) double bond and lack γ-lactone. The cytotoxic activities of compounds 1–7 against mouse neuroblastoma Neuro 2a, normal epithelial JB-6 cells and erythrocytes were studied. Kuriloside A₁ (1) was the most active compound in the series, demonstrating strong cytotoxicity against the erythrocytes and JB-6 cells and a moderate effect against Neuro 2a cells.     

Can Some Marine-Derived Fungal Metabolites Become Actual Anticancer Agents?

Marine fungi are known to produce structurally unique secondary metabolites, and more than 1000 marine fungal-derived metabolites have already been reported. Despite the absence of marine fungal-derived metabolites in the current clinical pipeline, dozens of them have been classified as potential chemotherapy candidates because of their anticancer activity. Over the last decade, several comprehensive reviews have covered the potential anticancer activity of marine fungal-derived metabolites. However, these reviews consider the term “cytotoxicity” to be synonymous with “anticancer agent”, which is not actually true. Indeed, a cytotoxic compound is by definition a poisonous compound. To become a potential anticancer agent, a cytotoxic compound must at least display (i) selectivity between normal and cancer cells (ii) activity against multidrug-resistant (MDR) cancer cells; and (iii) a preferentially non-apoptotic cell death mechanism, as it is now well known that a high proportion of cancer cells that resist chemotherapy are in fact apoptosis-resistant cancer cells against which pro-apoptotic drugs have more than limited efficacy. The present review thus focuses on the cytotoxic marine fungal-derived metabolites whose ability to kill cancer cells has been reported in the literature. Particular attention is paid to the compounds that kill cancer cells through non-apoptotic cell death mechanisms.     

Bioactive 7-Oxabicyclic[6.3.0]lactam and 12-Membered Macrolides from a Gorgonian-Derived Cladosporium sp. Fungus

One new bicyclic lactam, cladosporilactam A (1), and six known 12-membered macrolides (2–7) were isolated from a gorgonian-derived Cladosporium sp. fungus collected from the South China Sea. Their complete structural assignments were elucidated by comprehensive spectroscopic investigation. Quantum chemistry calculations were used in support of the structural determination of 1. The absolute configuration of 1 was determined by calculation of its optical rotation. Cladosporilactam A (1) was the first example of 7-oxabicyclic[6.3.0]lactam obtained from a natural source. Compound 1 exhibited promising cytotoxic activity against cervical cancer HeLa cell line with an IC₅₀ value of 0.76 μM.     

A new cytotoxic sesquiterpene quinone produced by Penicillium sp. F00120 isolated from a deep sea sediment sample

A new fungal strain, displaying strong toxic activity against brine shrimp larvae, was isolated from a deep sea sediment sample collected at a depth of 1300 m. The strain, designated as F00120, was identified as a member of the genus Penicillium on the basis of morphology and ITS sequence analysis. One new sesquiterpene quinone, named penicilliumin A (1), along with two known compounds ergosterol (2) and ergosterol peroxide (3), were isolated and purified from the cultures of F00120 by silica gel column, Sephadex LH-20 column, and preparative thin layer chromatography. Their structures were elucidated by detailed nuclear magnetic resonance (NMR) and mass spectroscopic (MS) analysis as well as comparison with literature data. The new compound penicilliumin A inhibited in vitro proliferation of mouse melanoma (B16), human melanoma (A375), and human cervical carcinoma (Hela) cell lines moderately.     

不同感染剂量MDRV对番鸭免疫反应和细胞毒性作用的影响

用不同剂量番鸭呼肠孤病毒(MDRV MW9710株)感染8日龄番鸭后,通过检测血液中淋巴细胞对ConA、LPS的反应和NK细胞、细胞毒T细胞(CTL)的细胞毒性作用,探讨MDRV感染对番鸭免疫细胞功能和细胞毒性作用的影响。结果显示,不同感染剂量MDRV均会抑制番鸭血液淋巴细胞对ConA、LPS的增殖反应,降低NK细胞和CTL细胞的杀伤活性,且影响程度与剂量相关;同时感染番鸭生长缓慢,脾脏肿大,胸腺和法氏囊缩小。上述结果表明,MDRV感染能导致番鸭免疫抑制,且细胞免疫抑制程度与感染病毒量有关。     

表达MDVgB基因重组痘苗病毒的构建及保护性研究

以脂质体转染技术构建了表达鸡马立克氏病毒(MDV)gB基因的重组痘苗病毒(RVV-gB), 表明该病毒在CV-1(猴肾细胞)细胞系内能稳定传代,经腹腔1×106 PFU·羽 -1 将重组病毒、HVT冻干苗及痘苗病毒分别按试验程序,免疫1日龄SPF鸡,并于15日龄以3×10 2PFU·羽-1MDV强毒株GA株攻毒,重组病毒和HVT冻干苗匀获得较高的保护, 结果证明了gB是MDV的宿主保护性抗原.此研究为CTL应答检测奠定了基础.     

厚叶软珊瑚化学成分及其细胞毒活性研究

利用多种层析方法,从厚叶软珊瑚φ=95%的乙醇提取物中获得4个化合物,通过理化性质测定和波谱分析,分别鉴定为鲨肝醇(11)、2-十六烷酸甘油酯(12)、十六烷酸乙酯(13)、5,8,11,14二十碳四烯酸酸甲酯(14),其中化合物11~14均为首次从该种中发现。对从厚叶软珊瑚获得的部分纯化合物1~10进行初步的细胞毒活性测试,结果表明,化合物4~6对人肝癌细胞株、人肺腺癌细胞株和血管内皮细胞的细胞毒性有一定的特异性,而对正常细胞的毒性较低。     

Inhibitory effects of seaweeds on histamine release from rat basophile leukemia cells (RBL-2H3)

ABSTRACT:   The effects of 80% methanol extracts from frozen samples of 41 macroalgae and one sea grass collected in the Ise-Shima region of Japan were investigated on histamine release from rat basophile leukemia cells (RBL-2H3) sensitized with antidinitrophenyl (DNP) IgE and stimulated with DNP-BSA. Of the 21 brown algae, five green and 15 red algae, and one sea grass tested, only extracts from seven brown algae suppressed histamine release from RBL cells, as determined by high-performance liquid chromatography (HPLC) analysis. When the cytotoxic effects of the seven brown algal extracts were investigated by Trypan blue staining, only Eisenia arborea and Sargassum thunbergii did not show cytotoxic effects. Therefore, we conclude that E. arborea and S. thunbergii may contain compounds that have antiallergic effects without inducing cell death.