Synthesis and Evaluation of Some New Aza-B-homocholestane Derivatives as Anticancer Agents

Using analogues of some marine steroidal oximes as precursors, a series of aza-B-homocholestane derivatives possessing different substituted groups at the 3-position of the steroidal nucleus were synthesized. Their biological activity against cancer cell proliferation was determined with multiple cancer cell lines. Aza-B-homocholestane derivatives possessing 3-hydroxyl, 3-hydroximino and 3-thiosemicarbazone groups displayed remarkable cytotoxicity to cancer cells via apoptosis inducing mechanism. Compounds 5, 10, 12, 15 and 18 exhibited better potency to inhibit cancer cell proliferation. In addition, compound 15 was further evaluated with three dimensional (3D) multicellular spheroids assay to determine its potency against spheroid growth. The structure-activity relationship (SAR) generated in the studies is valuable for the design of novel chemotherapeutic agents.     

Marine Sponge Derived Natural Products between 2001 and 2010: Trends and Opportunities for Discovery of Bioactives

Marine sponges belonging to the phylum Porifera (Metazoa), evolutionarily the oldest animals are the single best source of marine natural products. The present review presents a comprehensive overview of the source, taxonomy, country of origin or geographical position, chemical class, and biological activity of sponge-derived new natural products discovered between 2001 and 2010. The data has been analyzed with a view to gaining an outlook on the future trends and opportunities in the search for new compounds and their sources from marine sponges.     

太岁的研究进展

太岁是一种多菌类复合体,其生物活性成分在抗癌、抗菌、细胞毒性及生理调控等方面具有重要功能.由于生物技术限制,目前对不同太岁样品的生物活性成分及菌群结构只做了初步分析,通过多种方式分离鉴定太岁菌种构成,对做好太岁的资源化利用具有重要的意义,现在距规模化开发利用太岁还有许多开创性的工作要做.通过综述太岁的微生物组成、药用价值、生物活性成分及其在微生态制剂方面的应用,对太岁应用前景进行展望,以期为太岁的进一步研究与利用提供借鉴法.     

芳香型二丁基锡双羧酸酯的合成、表征及抗癌活性研究

用二正丁基氧化锡和取代芳香单羧酸以1∶2摩尔比反应,合成了10个芳香型二正丁基锡双羧酸酯n-Bu2Sn(OOCAr)2(3a~3j).利用1H NMR,119Sn NMR和IR等对这些化合物进行了表征.并用X-射线单晶衍射测定了其中化合物3b和3e的晶体结构.3b和3e晶体中锡原子配位数均为6,形成了严重扭的曲八面体几何构型.3b和3e均存在分子内及分子间氢键作用,3b中氢键作用较弱,在生物体系中比3e更易释放出游离态R2Sn2 ,易与癌细胞的DNA结合,具有更好的抗癌生物活性.     

Extract from the Zooxanthellate Jellyfish Cotylorhiza tuberculata Modulates Gap Junction Intercellular Communication in Human Cell Cultures

On a global scale, jellyfish populations in coastal marine ecosystems exhibit increasing trends of abundance. High-density outbreaks may directly or indirectly affect human economical and recreational activities, as well as public health. As the interest in biology of marine jellyfish grows, a number of jellyfish metabolites with healthy potential, such as anticancer or antioxidant activities, is increasingly reported. In this study, the Mediterranean “fried egg jellyfish” Cotylorhiza tuberculata (Macri, 1778) has been targeted in the search forputative valuable bioactive compounds. A medusa extract was obtained, fractionated, characterized by HPLC, GC-MS and SDS-PAGE and assayed for its biological activity on breast cancer cells (MCF-7) and human epidermal keratinocytes (HEKa). The composition of the jellyfish extract included photosynthetic pigments, valuable ω-3 and ω-6 fatty acids, and polypeptides derived either from jellyfish tissues and their algal symbionts. Extract fractions showed antioxidant activity and the ability to affect cell viability and intercellular communication mediated by gap junctions (GJIC) differentially in MCF-7and HEKa cells. A significantly higher cytotoxicity and GJIC enhancement in MCF-7 compared to HEKa cells was recorded. A putative action mechanism for the anticancer bioactivity through the modulation of GJIC has been hypothesized and its nutraceutical and pharmaceutical potential was discussed.     

Evidence of Anti-Proliferative Activities in Blue Mussel (Mytilus edulis) By-Products

Shellfish waste components contain significant levels of high quality protein and are therefore a potential source for biofunctional high-value peptides. The feasibility of applying a pilot scale enzymatic hydrolysis process to whole Mytilus edulis and, by fractionation, recover hydrolysates presenting a biological activity of interest, was evaluated. Fractions were tested on four immortalized cancerous cell lines: A549, BT549, HCT15 and PC3. The 50 kDa fraction, enriched in peptides, presented anti-proliferative activity with all cell lines and results suggest a bioactive molecule synergy within the fraction. At a protein concentration of 44 µg/mL, the 50 kDa fraction induced a mortality of 90% for PC3, 89% for A549, 85% for HCT15 and of 81% for BT549 cell lines. At the low protein concentration of only 11 µg/mL the 50 kDa fraction still entails a cell mortality of 76% for A549 and 87% for PC3 cell lines. The 50 kDa fraction contains 56% of proteins, 3% of lipids and 6% of minerals on a dry weight basis and the lowest levels detected of taurine and methionine and highest levels of threonine, proline and glycine amino acids. The enzymatic hydrolysis process suggests that Mytilus edulis by-products should be viewed as high-valued products with strong potential as anti-proliferative agent and promising active ingredients in functional foods.     

柚皮素的提取及其抗癌作用研究进展

指出了柚皮素属于二氢黄酮类天然化合物,是柚皮苷的苷元,具有重要的抗炎、抗菌、抗氧化、抗癌等生物学效应。柚皮素的提取方法有酸水解法、酶提取法、超临界CO_2提取法。柚皮素能作用于多种癌细胞,抑制其生长、增殖、迁移,并促进其凋亡,表现出抗癌活性。综述了柚皮素的提取和作用于不同类型的癌细胞的抗癌分子机制,并展望了量子化学技术在柚皮素抗癌作用靶向点的相互作用理论计算研究的应用前景。     

A dose‐escalation study of combretastatin A4‐phosphate in healthy dogs

Combretastatin A4 ‐Phosphate (CA4P ) is a vascular disrupting agent revealing promising results in cancer treatments for humans. The aim of this study was to investigate the safety and adverse events of CA4P in healthy dogs as a prerequisite to application of CA4P in dogs with cancer. Ten healthy dogs were included. The effects of escalating doses of CA4P on physical, haematological and biochemical parameters, systolic arterial blood pressure, electrocardiogram, echocardiographic variables and general wellbeing were characterised. Three different doses were tested: 50, 75 and 100 mg m^?2. At all 3 CA4P doses, nausea, abdominal discomfort as well as diarrhoea were observed for several hours following administration. Likewise, a low‐grade neutropenia was observed in all dogs. Doses of 75 and 100 mg m^?2 additionally induced vomiting and elevation of serum cardiac troponine I levels. At 100 mg m^?2, low‐grade hypertension and high‐grade neurotoxicity were also observed. In healthy dogs, doses up to 75 mg m^?2 seem to be well tolerated. The severity of the neurotoxicity observed at 100 mg m^?2, although transient, does not invite to use this dose in canine oncology patients.     

茶叶及其儿茶素类对乳腺癌的抑制作用

茶叶对人体健康有众多益处是因为它富含儿茶素类化合物。茶叶中的儿茶素类化合物有10种以上,其中含量最高的是表没食子儿茶素没食子酸酯(EGCG)。许多研究表明,以EGCG为代表的茶叶儿茶素类化合物对乳腺癌具有抑制作用,其作用包括:抑制致癌物诱导的活性氧自由基(ROS)升高及其引起的DNA损伤、降低细胞对肿瘤坏死因子的响应、阻碍雌激素与雌激素受体的结合、抑制DNA甲基化、保护线粒体免受氧化损伤、抑制肿瘤血管生成、减少癌细胞的转移和增殖、改善代谢综合征以减少抗癌药物副作用、与抗癌药物产生协同效应等。本文综述了该研究领域的进展,并讨论导致研究结果不一致的原因和未来的研究方向。     

Cyanobacterial Metabolite Calothrixins: Recent Advances in Synthesis and Biological Evaluation

The marine environment is host to unparalleled biological and chemical diversity, making it an attractive resource for the discovery of new therapeutics for a plethora of diseases. Compounds that are extracted from cyanobacteria are of special interest due to their unique structural scaffolds and capacity to produce potent pharmaceutical and biotechnological traits. Calothrixins A and B are two cyanobacterial metabolites with a structural assembly of quinoline, quinone, and indole pharmacophores. This review surveys recent advances in the synthesis and evaluation of the biological activities of calothrixins. Due to the low isolation yields from the marine source and the promise this scaffold holds for anticancer and antimicrobial drugs, organic and medicinal chemists around the world have embarked on developing efficient synthetic routes to produce calothrixins. Since the first review appeared in 2009, 11 novel syntheses of calothrixins have been published in the efforts to develop methods that contain fewer steps and higher-yielding reactions. Calothrixins have shown their potential as topoisomerase I poisons for their cytotoxicity in cancer. They have also been observed to target various aspects of RNA synthesis in bacteria. Further investigation into the exact mechanism for their bioactivity is still required for many of its analogs.