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。     

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.     

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.     

Marine Anticancer Agents: An Overview with a Particular Focus on Their Chemical Classes

The marine environment is a rich source of biologically active molecules for the treatment of human diseases, especially cancer. The adaptation to unique environmental conditions led marine organisms to evolve different pathways than their terrestrial counterparts, thus producing unique chemicals with a broad diversity and complexity. So far, more than 36,000 compounds have been isolated from marine micro- and macro-organisms including but not limited to fungi, bacteria, microalgae, macroalgae, sponges, corals, mollusks and tunicates, with hundreds of new marine natural products (MNPs) being discovered every year. Marine-based pharmaceuticals have started to impact modern pharmacology and different anti-cancer drugs derived from marine compounds have been approved for clinical use, such as: cytarabine, vidarabine, nelarabine (prodrug of ara-G), fludarabine phosphate (pro-drug of ara-A), trabectedin, eribulin mesylate, brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, belantamab mafodotin, plitidepsin, and lurbinectedin. This review focuses on the bioactive molecules derived from the marine environment with anticancer activity, discussing their families, origin, structural features and therapeutic use.     

Design and Synthesis of Novel Phenylahistin Derivatives Based on Co-Crystal Structures as Potent Microtubule Inhibitors for Anti-Cancer Therapy

Phenylahistin is a naturally occurring marine product with a diketopiperazine structure that can bind to the colchicine site of microtubulin as a possible anticancer agent. To develop more potent microtubule inhibitors, novel phenylahistin derivatives were designed and synthesized based on the co-crystal complexes of phenylahistin derivatives and microtubulin. We established a focused library of imidazole-type molecules for the introduction of different groups to the C-ring and A-ring of phenylahistin. Structure–activity relationship studies indicated that appropriate hydrocarbon substituents and unsaturated alkenyl substituents at the 1-position of the imidazole group are important for improving the activity of such compounds. In addition, this study found that propylamine groups could maintain the activity of these compounds, as exemplified by compound 16d (IC₅₀ = 5.38 nM, NCI-H460). Compound 15p (IC₅₀ = 1.03 nM, NCI-H460) with an allyl group exhibited potent cytotoxic activity at the nanomolar level against human lung cancer cell lines. Immunofluorescence assay indicated that compound 15p could efficiently inhibited microtubule polymerization and induced a high expression of caspase-3. 15p also displayed good pharmacokinetic characteristics in vitro. Additionally, the growth of H22 transplanted tumors was significantly inhibited in BALB/c mice when 15p alone was administered at 4 mg/kg, and the tumor inhibition rate was as much as 65%. Importantly, the continuous administration of 15p resulted in a lower toxicity than that of docetaxel (10 mg/kg) and cyclophosphamide (20 mg/kg). Overall, the novel allyl-imidazole-diketopiperazine-type derivatives could be considered safe and effective potential agents for cancer treatment.     

A New Bioassay Platform Design for the Discovery of Small Molecules with Anticancer Immunotherapeutic Activity

Immunotherapy takes advantage of the immune system to prevent, control, and eliminate neoplastic cells. The research in the field has already led to major breakthroughs to treat cancer. In this work, we describe a platform that integrates in vitro bioassays to test the immune response and direct antitumor effects for the preclinical discovery of anticancer candidates. The platform relies on the use of dendritic cells that are professional antigen-presenting cells (APC) able to activate T cells and trigger a primary adaptive immune response. The experimental procedure is based on two phenotypic assays for the selection of chemical leads by both a panel of nine tumor cell lines and growth factor-dependent immature mouse dendritic cells (D1). The positive hits are then validated by a secondary test on human monocyte-derived dendritic cells (MoDCs). The aim of this approach is the selection of potential immunotherapeutic small molecules from natural extracts or chemical libraries.     

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。     

Natural Polyether Ionophores and Their Pharmacological Profile

This review is devoted to the study of the biological activity of polyether ionophores produced by bacteria, unicellular marine algae, red seaweeds, marine sponges, and coelenterates. Biological activities have been studied experimentally in various laboratories, as well as data obtained using QSAR (Quantitative Structure–Activity Relationships) algorithms. According to the data obtained, it was shown that polyether toxins exhibit strong antibacterial, antimicrobial, antifungal, antitumor, and other activities. Along with this, it was found that natural polyether ionophores exhibit such properties as antiparasitic, antiprotozoal, cytostatic, anti-mycoplasmal, and antieczema activities. In addition, polyethers have been found to be potential regulators of lipid metabolism or inhibitors of DNA synthesis. Further study of the mechanisms of action and the search for new polyether ionophores and their derivatives may provide more effective therapeutic natural polyether ionophores for the treatment of cancer and other diseases. For some polyether ionophores, 3D graphs are presented, which demonstrate the predicted and calculated activities. The data presented in this review will be of interest to pharmacologists, chemists, practical medicine, and the pharmaceutical industry.     

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.     

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.