海洋活性物质Fascaplysin及衍生物的化学合成与构效关系研究进展

海洋活性物质Fascaplysin是从海绵中发现的一种具有抑制肿瘤细胞增殖的吲哚生物碱类化合物。对细胞周期蛋白依赖性激酶CDKs尤其是CDK4／D1具有特异性抑制,同时Faseaplysln因其平面芳香稠环结构对DNA有嵌入作用,能够改变DNA的构象从而阻止DNA的复制。本文主要阐述Fascaplysin与CDKs作用的机制,以及Fascaplysin的毒副作用,进而探讨副作用小的Fascaplysin衍生物的合成方向。     

天然3-烃基黄酮及其生物活性研究进展

本文概述了已发现的具有生物活性的天然3-烃基黄酮类化合物及其生物活性包括抗爱滋病病毒、抗肿瘤、抑制血小板、抑制环磷酸二酯酶等作用.     

表没食子儿茶素没食子酸酯研究进展

近些年发现,茶叶中的表没食子儿茶素没食子酸脂具有降低血脂、除去胆固醇、抑制细菌和病毒、抗氧化、抗突变、抗肿瘤等多方面的重要生理功能。     

食用菌活性成分抗肿瘤作用的研究进展

食用菌因药食两用的特点被广泛研究,具有提升机体免疫,阻止和防御疾病的功能作用。不同食用菌中所含的生物活性组分不同,主要有:多糖类、蛋白类、萜类、生物碱类等,这些组分具有抗氧化、抗肿瘤、免疫调节、抗炎症反应、抗心血管疾病、抗细菌、抗辐射及抗糖尿病等功效,其中抗肿瘤作用研究居多,研究发现其分子作用机制主要通过调控细胞信号通路中相关因子表达水平抑制肿瘤细胞增殖,诱导细胞凋亡的,这为开发天然无毒性肿瘤药物制剂奠定了理论基础。针对食用菌不同生物活性组分抗肿瘤分子机制的最新研究进展展开简要综述。     

姜黄素抗肿瘤作用及机制研究进展

姜黄素是从草本植物姜黄、莪术等根茎中提取的一种植物多酚,有着广泛的药理作用,具有抗心血管疾病、抗肿瘤、抗微生物、抗抑郁、抗炎、抗氧化等生物学功能。抗肿瘤是姜黄素主要生物活性之一,抗肿瘤机制主要有:抑制肿瘤细胞增殖,诱导肿瘤细胞凋亡,抗肿瘤侵袭及转移,逆转肿瘤细胞耐药性及增加对化疗的敏感性等。本文就其抗肿瘤机制的研究进行综述,为姜黄素的进一步开发利用提供基础。     

肝素的抗肿瘤转移活性及其与选凝素的关系

肝素作为传统抗凝剂,常用来治疗癌症患者静脉血栓。临床和实验数据证实,肝素具有抗肿瘤活性。同时也有大量研究发现,肝素有抗肿瘤转移的作用。肝素可以通过各种机制抑制肿瘤转移,包括抑制细胞间的相互作用;抑制肝素酶的表达;调节各种生长因子以及调节机体凝血功能等。选凝素(seletin)是介导肿瘤转移初始阶段的重要因子,而肝素能够抑制选凝素介导的的肿瘤细胞与白细胞、血小板及内皮细胞的相互作用,从而达到抗转移的效果。本文综述了肝素抑制选凝素介导的肿瘤转移的作用机制,为肝素在抗肿瘤转移方面的临床应用提供参考。     

白皮杉醇抗肿瘤作用研究进展

白皮杉醇是一种化学结构类似于白藜芦醇的天然小分子化合物,具有抗氧化、清除自由基、抗菌、抗炎、抗白血病、抗细胞增殖、提高免疫调节能力、抗癌、防癌等生物活性。白皮杉醇的抗氧化、抗侵袭等生物活性强于白藜芦醇,而其抗肿瘤作用机制尚未明确。近年,白皮杉醇在抑制肿瘤细胞增殖、诱导肿瘤细胞凋亡及抑制肿瘤细胞侵袭和迁移方面的作用越来越受到广泛关注,本文通过文献查阅后对白皮杉醇抗肿瘤作用的最新研究进展进行归纳总结,旨在为白皮杉醇进一步开发成抗肿瘤药物奠定理论基础和实验依据。     

甘草甜素抗炎及抗肿瘤机制研究进展

甘草甜素是中药甘草的主要成分,具有抗炎、抗病毒、抗肿瘤等作用,随着研究的不断深入,甘草甜素广泛地应用于银屑病、慢性肝病、艾滋病及肿瘤等疾病的治疗中。近年来,学者对其抗炎和抗肿瘤作用研究较为突出,其机制包括抑制炎症因子、抗氧化、免疫调节、抗血管生成等,为更好地指导临床应用,就目前甘草甜素抗炎和抗肿瘤机制作一综述。     

丹参酮抗肿瘤研究新进展

丹参酮是一类从传统中药材丹参中提取的醌类化合物,近年研究发现其具有多种生物活性,包括抗氧化,抗炎,抑制增殖,诱导凋亡等作用,本文针对丹参酮自2008年至今的国内外抗肿瘤研究进行综述。     

花青素抗消化道肿瘤的作用机制研究进展

消化道恶性肿瘤的发病率和死亡率均居世界前列。花青素属于酚类化合物中的黄酮类化合物,具有抗氧、抗炎、抗肿瘤、预防心血管疾病等活性。通过对花青素以往的研究,从抗氧化、抗炎、阻滞细胞周期、促进肿瘤细胞凋亡及抑制肿瘤转移和血管生成等方面对其在抗肿瘤领域的进展进行综述。     

Synthesis of C4-fluorinated solamins and their growth inhibitory activity against human cancer cell lines

C4-Fluorinated analogues of solamin, an antitumor acetogenin, were synthesized and investigated for their antitumor activities against 39 tumor cell lines. C4-Fluorinated solamins showed more potent growth inhibitory activity against cancer cell lines than solamin.     

Synthesis of 1-beta-D-ribofuranosyl-1,2-dihydropyrimidin-2-one derivatives and their biological activities

Several alkyl substituted 1-beta-D-ribofuranosyl-1,2-dihydropyrimidin-2-one derivatives were synthesized by the method of stannic chloride-catalyzed glycosidation method to elucidate their inhibitory activity of cytidine deaminase and also their antitumor activities in vitro and in vivo. Alkyl substitution at position 4 or 6 of the derivatives decreased their inhibitory activity for cytidine deaminase and also decreased antitumor activity against L1210 cells in vitro.     

Human platelet factor 4 is a direct inhibitor of human osteoblast-like osteosarcoma cell growth.

The effect of purified human platelet factor 4, a platelet alpha-granule protein, on the growth of the human osteoblastic osteosarcoma cell lines Saos-2 and G-292 was investigated. Platelet factor 4 (20 ng/ml to 2 micrograms/ml) caused a significant, dose-dependent inhibition of human osteoblast-like osteosarcoma cell proliferation. Platelet factor 4 exerted its inhibitory effect under all growth conditions tested: serum-free, serum-stimulated and thrombin-stimulated. The platelet factor 4-induced cell inhibition was not associated with a cytotoxic effect on the cells (assessed by lactate dehydrogenase release). The inhibitory effect of platelet factor 4 was not affected by the presence of indomethacin in the cultures, indicating that the effect was prostaglandin-independent. These results suggest that platelet factor 4 has direct antitumor effects and that it may be important in pathological and physiological processes of bone.     

Discovery of a novel class of 2-aminopyrimidines as CDK1 and CDK2 inhibitors

A series of new 2-(2-aminopyrimidin-4-yl)phenol derivatives were synthesized as potential antitumor compounds. Substitution with pyrrolidine-3,4-diol at the 4-position of phenol provided potent inhibitory activity against CDK1 and CDK2. X-ray crystal structural studies were performed to account for the effect of the substituent on both the enzymatic and cell growth inhibitory activities.     

Four-membered heterocycles-containing 4-anilino-quinazoline derivatives as epidermal growth factor receptor (EGFR) kinase inhibitors

We report herein the design and synthesis of novel azaspirocycle or azetidine substituted 4-anilinoquinazoline derivatives. The EGFR inhibitory activities and in vitro antitumor potency of these newly synthesized compounds against two lung cancer cell lines HCC827 and A549 were evaluated. Most of the target compounds possess good inhibitory potency. In particular, compounds 21g with 2-oxa-6-azaspiro[3.4]octane substituent was found to possess higher EGFR inhibitory activities and similar antitumor potency comparing to the lead compound gefitinib with improved water solubility.     

Design,synthesis and biological evaluation of novel antitumor spirodihydrothiopyran-oxindole derivatives

Sulfur containing spiroheterocyclic oxindoles are promising privileged scaffolds in medicinal chemistry and drug discovery. Previously, we identified a new class of spirodihydrothiopyran-oxindoles with good in vitro antitumor activity against A549 lung cancer cell line. Herein, various spirooxindole-dihydrothiopyrans with diverse substitutions were synthesized and assayed to investigate the structure-activity relationships. Among the derivatives, compounds 4b, 4i, 4m, 4n and 4q displayed superior or comparable antitumor activity than nutlin-3. Molecular mechanism study revealed this scaffold displayed moderate MDM2 inhibitory activity, significantly induced cancer cell apoptosis and arrested cell cycle at G0/G1 phase, which represented a good lead compound for antitumor drug discovery.     

A new C-nucleoside analogue of tiazofurin: synthesis and biological evaluation of 2-beta-D-ribofuranosylimidazole-4-carboxamide (imidazofurin)

2-Beta-D-ribofuranosylimidazole-4-carboxamide, an imidazole analogue of the antitumor agent tiazofurin, was synthesized and evaluated for the growth inhibitory activity of human myelogenous leukemia K562 cells.     

Arylsulfonyl-N,N-dialkyl-dithiocarbamates as tumor cell growth inhibitors: novel agents targeting beta-tubulin?

Reaction of sodium N,N-dimethyldithiocarbamate or N,N-diethyldithiocarbamate with arylsulfonyl halides afforded a series of arylsulfonyl-N,N-dialkyl-dithiocarbamates. The reactivity of these new derivatives with cysteine and glutathione has been investigated in order to identify derivatives that might label a cysteine residue of the heterodimeric protein tubulin which plays a critical physiological function in cell division and also possesses enzymatic activity as a GTP-ase. Since many antitumor drugs exert their action by binding to tubulin, inhibiting in this way microtubule association and provoking cell death, some of the most reactive compounds against the thiol reagents found in this work have been assayed for their antitumor activity. Indeed strong tumor cell growth inhibitory properties against several leukemia, non-small cell lung, ovarian, melanoma, colon, CNS, renal, prostate and breast cancer has been found in vitro for some of the 4-halogeno-, 4-methyl- or 4-carboxyphenyl-substituted arylsulfonyl-N,N-dialkyl-dithiocarbamates. Furthermore, some of these derivative were shown to act as in vitro tubulin polymerization inhibitors using a turbidimetric assay.