基于天蚕素A和胡蜂毒素的杂合肽设计及活性鉴定

为了进一步改善胡蜂毒素（mastoparan,MP）的抗菌、抗肿瘤活性并减少细胞毒性,本研究通过分子杂合方法对其进行改造,并初步鉴定设计的杂合多肽的生物活性。以天蚕素A的N-端1-8序列片段和胡蜂毒素的保守序列为模板进行杂合设计,获得一条新型杂合肽KL-21。以胡蜂毒素MP-L作为参照,采用生物信息学方法、微量倍比稀释法、杀菌动力学方法、溶血试验、CCK-8法分别对KL-21和MP-L进行理化参数分析、结构预测、最小抑菌浓度（MIC）和最小杀菌浓度（MBC）测定、杀菌动力学研究、溶血活性测定及肿瘤细胞毒性试验。结果表明,KL-21可以在短时间内迅速杀灭细菌,对革兰氏阳性菌（金黄色葡萄球菌）和阴性菌（大肠杆菌）的MIC均为4~8 μg/mL,MBC均为8~16 μg/mL;KL-21对真菌（白色念珠菌）的最小MIC为32 μg/mL,MBC为64 μg/mL。兔红细胞溶血试验表明,KL-21在128 μg/mL时溶血活性仅为20%,较MP-L的溶血活性明显降低。细胞毒性试验表明,KL-21对肺癌细胞A549具有良好的抑制作用,16 μg/mL的体外抑制率达86%。研究表明,新型杂合肽KL-21较MP-L的抗菌和抗肿瘤活性有较大提高,细胞毒性显著降低,可以作为先导肽进一步研究和开发。     

新型抗癌配合物的研究——Ⅰ钯(Ⅱ)—邻二氮菲—氨基酸配合物的抗癌活性

本文合成了三种新的钯(Ⅰ)—邻二氮菲—氨基酸配合物〔Pd(phen)AA〕C1, AA为L-赖氨酸,L-脯氨酸,L-精氨酸.用元素分析、红外光谱等方法对配合物进行表征,用细胞染料排斥法、动物实验考察了配合物的抗癌活性.结果表明,以上三种配合物均具有不同程度的抗癌活性,且较顺铂优越之处在于毒性很低,L-脯氨酸和L-精氨酸配合物的溶解度较好.     

Synthesis and Antiproliferative Activity of 2,5-bis(3′-Indolyl)pyrroles,Analogues of the Marine Alkaloid Nortopsentin

2,5-bis(3′-Indolyl)pyrroles, analogues of the marine alkaloid nortopsentin, were conveniently prepared through a three step procedure in good overall yields. Derivatives 1a and 1b exhibited concentration-dependent antitumor activity towards a panel of 42 human tumor cell lines with mean IC₅₀ values of 1.54 μM and 0.67 μM, respectively. Investigating human tumor xenografts in an ex-vivo clonogenic assay revealed selective antitumor activity, whereas sensitive tumor models were scattered among various tumor histotypes.     

中药诱导肿瘤细胞凋亡机制研究进展

中药及其生物活性成分具有毒副作用小、无残留、药理作用独特等特点,在抗肿瘤研究方面,已经成为抗肿瘤药物或其辅助药物,目前研究的热点是中药治疗肿瘤作用机制的研究。论文从单味中药及其有效成分、中药复方诱导肿瘤细胞凋亡机制等方面对中药诱导细胞凋亡在肿瘤的发生、发展和转归中所起的作用进行了综述。中药可以诱导肿瘤细胞凋亡,其可能的作用机制是通过调控原癌基因和抑癌基因的表达、影响细胞凋亡通路的信号传导及阻滞肿瘤细胞增殖周期等抑制肿瘤细胞的永生化。     

Study on the Structure of Two New Bioactive Peptides from Rana catesbeiana and their Antitumor Effects in vitro

The study was aimed to research the growth inhibitory effects of two new bioactive peptides Temporin-Lb and Catesbeianin-1a from Rana catesbeiana on human lung cancer NCI-H446 cells, breast cancer MCF-7 cells and mice leukemia K562 cells, and provide the basis for selecting the new peptide antitumor drugs.The second structures of two bioactive peptides were tested by circular dichroism spectrum (CD), and the effects of the two new bioactive peptides on human lung cancer NCI-H446 cells, breast cancer MCF-7 cells and mice leukemia K562 cells were examined with MTS cytotoxicity assay.The circular dichroism spectrum results showed the secondary structure of Temporin-Lb was PPⅡ, and the secondary structure of Catesbeianin-1a was random coil.Using MTS cytotoxicity assay, it was found that given Catesbeianin-1a, the sharp of the three cancer cells above had little changed after culturing for 24 h, and the three cancer cells promoted normal.Given Temporin-Lb, the cell morphology of three cancer cells had changed after culturing for 24 h, the growth of the three cancer cells above had been inhibited, especially the bioactive peptide Temporin-Lb had a sharp antitumor effect to mice leukemia K562 cells between the concentration of 4 and 40 μmol/L.Bioactive peptide Catesbeianin-1a had no obvious effect on proliferation of the three cancer cells above.Bioactive peptide Temporin-Lb had a certain inhibitory effect to tumor cells.     

A Chemoinformatics Approach to the Discovery of Lead-Like Molecules from Marine and Microbial Sources En Route to Antitumor and Antibiotic Drugs

The comprehensive information of small molecules and their biological activities in the PubChem database allows chemoinformatic researchers to access and make use of large-scale biological activity data to improve the precision of drug profiling. A Quantitative Structure–Activity Relationship approach, for classification, was used for the prediction of active/inactive compounds relatively to overall biological activity, antitumor and antibiotic activities using a data set of 1804 compounds from PubChem. Using the best classification models for antibiotic and antitumor activities a data set of marine and microbial natural products from the AntiMarin database were screened—57 and 16 new lead compounds for antibiotic and antitumor drug design were proposed, respectively. All compounds proposed by our approach are classified as non-antibiotic and non-antitumor compounds in the AntiMarin database. Recently several of the lead-like compounds proposed by us were reported as being active in the literature.     

Antitumor peptides from marine organisms

The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited resource of new antitumor agents in the field of the development of marine bioactive substances. In this review, the progress on studies of antitumor peptides from marine sources is provided. The biological properties and mechanisms of action of different marine peptides are described; information about their molecular diversity is also presented. Novel peptides that induce apoptosis signal pathway, affect the tubulin-microtubule equilibrium and inhibit angiogenesis are presented in association with their pharmacological properties. It is intended to provide useful information for further research in the fields of marine antitumor peptides.     

Important determinants for fucoidan bioactivity: a critical review of structure-function relations and extraction methods for fucose-containing sulfated polysaccharides from brown seaweeds

Seaweeds--or marine macroalgae--notably brown seaweeds in the class Phaeophyceae, contain fucoidan. Fucoidan designates a group of certain fucose-containing sulfated polysaccharides (FCSPs) that have a backbone built of (1→3)-linked α-L-fucopyranosyl or of alternating (1→3)- and (1→4)-linked α-L-fucopyranosyl residues, but also include sulfated galactofucans with backbones built of (1→6)-β-D-galacto- and/or (1→2)-β-D-mannopyranosyl units with fucose or fuco-oligosaccharide branching, and/or glucuronic acid, xylose or glucose substitutions. These FCSPs offer several potentially beneficial bioactive functions for humans. The bioactive properties may vary depending on the source of seaweed, the compositional and structural traits, the content (charge density), distribution, and bonding of the sulfate substitutions, and the purity of the FCSP product. The preservation of the structural integrity of the FCSP molecules essentially depends on the extraction methodology which has a crucial, but partly overlooked, significance for obtaining the relevant structural features required for specific biological activities and for elucidating structure-function relations. The aim of this review is to provide information on the most recent developments in the chemistry of fucoidan/FCSPs emphasizing the significance of different extraction techniques for the structural composition and biological activity with particular focus on sulfate groups.     

Quinazolin-4-one coupled with pyrrolidin-2-iminium alkaloids from marine-derived fungus Penicillium aurantiogriseum

Three new alkaloids, including auranomides A and B (1 and 2), a new scaffold containing quinazolin-4-one substituted with a pyrrolidin-2-iminium moiety, and auranomide C (3), as well as two known metabolites auranthine (4) and aurantiomides C (5) were isolated from the marine-derived fungus Penicillium aurantiogriseum. The chemical structures of compounds 1-3 were elucidated by extensive spectroscopic methods, including IR, HRESIMS and 2D NMR spectroscopic analysis. The absolute configurations of compounds 1-3 were suggested from the perspective of a plausible biosynthesis pathway. Compounds 1-3 were subjected to antitumor and antimicrobial screening models. Auranomides A-C exhibited moderate cytotoxic activity against human tumor cells. Auranomides B was the most potent among them with an IC(50) value of 0.097 μmol/mL against HEPG2 cells.