Synthesis and Anti-Cancer Activity of New Pyrazolinyl-Indole Derivatives: Pharmacophoric Interactions and Docking Studies for Identifying New EGFR Inhibitors

Newly designed series of indole-containing pyrazole analogs, pyrazolinylindoles, were synthesized, and their structures were confirmed based on the spectral data of the ¹H NMR, ¹³C NMR, and HR-MS analyses. Preliminary anti-cancer activity testings were carried out by the National Cancer Institute, United States of America (NCI, USA). Compounds HD02, HD05, and HD12 demonstrated remarkable cytotoxic activities against nine categories of cancer types based cell line panels which included leukemia, colon, breast, melanoma, lungs, renal, prostate, CNS, and ovarian cancer cell lines. The highest cytotoxic effects were exhibited by the compounds HD02 [1-(5-(1-H-indol-3-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenylethanone], HD05 [1-(3-(4-chlorophenyl)-5-(1H-indol-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenoxyethanone], and HD12 [(3-(4-chlorophenyl)-5-(1H-indol-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)(pyridin-4-yl)methanone] against some of the 56 types of NCI-based cell lines in different panels. Compound HD05 showed the maximum range of cancer cell growth inhibitions against all categories of the cell lines in all nine panels. On average, in comparison to the referral standard, imatinib, at a dose level of 10 µM, the HD05 showed significant activity against leukemia in the range of 78.76%, as compared to the imatinib at 9% of cancer cells’ growth inhibitions. Molecular docking simulation studies were performed in silico on the epidermal growth factor receptor (EGFR) tyrosine kinase, in order to validate the activity.     

Enhanced Anti-Cancer Effects of Conditioned Medium from Hypoxic Human Adult Dermal Fibroblasts on Cervical Cancer Cells

Hypoxia regulates fibroblast function by changing intracellular signaling and secretion factors, that influence the states of nearby cells. In this work, we investigated how medium (CM) from human adult dermal fibroblasts (HDFs) cultured in normoxic and hypoxic conditions affected cervical cancer (HeLa) cells. The HeLa cells showed decreased cell viability, increased apoptosis, and cell cycle arrest in response to CM from hypoxic-cultured HDFs (H-CM) compared with CM from normoxic-cultured HDFs (N-CM). Among the proteins up-regulated (>2-fold) in H-CM compared with N-CM, lymphotoxin-beta receptor (LTBR) decreased the viability of HeLa cells. Among the intracellular proteins down-regulated (>2-fold) in HeLa cells treated with H-CM compared with N-CM, the most enriched biological process GO term and KEGG pathway were protein deubiquitination and hsa05166:HTLV-I infection, respectively. In the protein–protein interaction network of intracellular proteins with altered expression (>2-fold), 1 up-regulated (TNF) and 8 down-regulated (ESR1, MCL1, TBP, CD19, LCK, PCNA, CHEK1, and POLA1) hub proteins were defined. Among the down-regulated hub proteins, the most enriched biological process GO term and KEGG pathway were leading strand elongation and hsa05166:HTLV-I infection, respectively. This study reveals that H-CM had stronger anti-cancer effects on cervical cancer cells than N-CM and induced intracellular signaling patterns related to those enhanced anti-cancer effects.     

Control the Silver Content in the Preparation Process of Platinum Group Anti-cancer Drugs

In order to control the silver content in the preparation process of platinum group anti-cancer drugs, we put two kinds of color reagent to color in the production process of the platinum anti-cancer drugs by UV spectra measurement to control drugs production of platinum anticancer, thus we could control the silver content in the drugs so that it meets the pharmacopoeia standards of US and European     

HPLC Method Research of Picoplatin-a New Platinum Anti-cancer Drug and Its Impurities

Purpose: To establish a HPLC testing method of the content of bulk picoplatin and its impurities. Method: the separation was perform on a C18 column(4.6 mm×250 mm, 5 m) with potassium dihydrogen phosphate-aceton-itrile as the mobile phase at a flow rate of 1.0 mL/min. The detecting wavelength was set at 210 nm, and the column temperature was set at 30℃. Result: in the method validation, the linear relationship modulus of picoplatin is 0.9999, the systemic precision is 0.44%, the method precision is 0.74%, the average recovery rate is 99.62%, the LOD and LOQ of picoplatin is 0.2 ng and 1.0 ng. The average resolution of picoplatin and its impurities is more than 2. Conclusion: The established method is good specificity, high sensitivity, and good repeatability which could provide scientific evidence for the quality control of picoplatin and its impurities.     

Cancer Cell Response to Anthracyclines Effects: Mysteries of the Hidden Proteins Associated with These Drugs

A comprehensive proteome map of T-lymphoblastic leukemia cells and its alterations after daunorubicin, doxorubicin and mitoxantrone treatments was monitored and evaluated either by paired comparison with relevant untreated control and using multivariate classification of treated and untreated samples. With the main focus on early time intervals when the influence of apoptosis is minimized, we found significantly different levels of proteins, which corresponded to 1%–2% of the total amount of protein spots detected. According to Gene Ontology classification of biological processes, the highest representation of identified proteins for all three drugs belong to metabolic processes of proteins and nucleic acids and cellular processes, mainly cytoskeleton organisation and ubiquitin-proteasome pathway. Importantly, we observed significant proportion of changes in proteins involved in the generation of precursor metabolites and energy typical for daunorubicin, transport proteins participating in response to doxorubicin and a group of proteins of immune system characterising response to mitoxantrone. Both a paired comparison and the multivariate evaluation of quantitative data revealed daunorubicin as a distinct member of the group of anthracycline/anthracenedione drugs. A combination of identified drug specific protein changes, which may help to explain anti-cancer activity, together with the benefit of blocking activation of adaptive cancer pathways, presents important approaches to improving treatment outcomes in cancer.     

基于网络药理学和分子对接探讨紫苏籽抗癌抗肿瘤的分子机制

采用网络药理学和分子对接的方法对紫苏籽成分、靶点、通路与癌症肿瘤的治疗进行系统研究。借助TCMSP、Genecards、Uniprot数据库收集紫苏籽成分、靶点以及癌症和肿瘤的靶点,使用Cytoscape软件构建紫苏籽成分、靶点与癌症肿瘤之间的网络图;通过STRING数据库进行蛋白互作网络分析,并借助DAVID平台进行GO功能和KEGG富集,采用Auto Dock将紫苏籽的活性成分和抗癌抗肿瘤靶点进行分子对接。结果表明：共筛选出紫苏籽抗癌抗肿瘤作用的靶点72个,对应17种有效成分。KEGG信号通路涉及的癌种包括膀胱癌、甲状腺癌、胰腺癌等。分子对接结果显示木犀草素和TP53对接活性最好。结论：该研究通过构建紫苏籽成分—靶点—疾病网络,挖掘紫苏籽抗癌抗肿瘤的关键靶点,并模拟靶点蛋白和活性成分的分子对接,为紫苏籽在临床应用及机制研究等方面提供了方向和思路。     

木瓜蛋白酶制备大豆抗癌活性肽的研究

以大豆分离蛋白为原料,以细胞生长抑制率为指标,用木瓜蛋白酶对其进行酶解,得到大豆抗癌活性肽。木瓜蛋白酶的最佳作用条件为:温度55℃、酶添加量7 000 U/g、反应pH 7.5、底物质量分数6%、酶解时间4 h。在抗癌活性肽制备过程中,对水解度和肽活性之间的关系进行了研究。结果表明,水解度与大豆肽的抗癌活性不呈线性关系。用10 000 u和5 000 u的超滤膜处理木瓜蛋白酶的酶解产物,在不同分子质量的超滤组分中,分子质量小于5 000 u组分的癌细胞生长抑制率最高,达32.58%。     

饱和脂肪酸的抗癌作用及其机制研究进展北大核心CSCD

饮食中的饱和脂肪酸通常与人体健康的负面影响相关,然而有关各种饱和脂肪酸的生理效应、生物功能等研究结果存在一定的争议。综述了饱和脂肪酸的可能抗癌作用及作用机制,以期为癌症的辅助治疗提供一定的参考。目前对短链饱和脂肪酸、中链饱和脂肪酸、奇数链饱和脂肪酸、支链饱和脂肪酸抗癌作用的报道较多,饱和脂肪酸主要通过阻滞细胞周期、诱导细胞凋亡、抑制细胞迁移和调控细胞生长相关的信号通路,或通过影响相关基因的表达和转录因子的磷酸化水平来发挥抗癌作用。     

Absorption,metabolism, anti-cancer effect and molecular targets of epigallocatechin gallate (EGCG): An updated review

Green tea is one of the most popular beverages in the world, especially in Asian countries. Consumption of green tea has been demonstrated to possess many health benefits, which mainly attributed to the main bioactive compound epigallocatechin gallate (EGCG), a flavone-3-ol polyphenol, in green tea. EGCG is mainly absorbed in the intestine, and gut microbiota play a critical role in its metabolism prior to absorption. EGCG exhibits versatile bioactivities, with its anti-cancer effect most attracting due to the cancer preventive effect of green tea consumption, and a great number of studies intensively investigated its anti-cancer effect. In this review, we therefore, first stated the absorption and metabolism process of EGCG, and then summarized its anti-cancer effect in vitro and in vivo, including its manifold anti-cancer actions and mechanisms, especially its anti-cancer stem cell effect, and next highlighted its various molecular targets involved in cancer inhibition. Finally, the anti-cancer effect of EGCG analogs and nanoparticles, as well as the potential cancer promoting effect of EGCG were also discussed. Understanding of the absorption, metabolism, anti-cancer effect and molecular targets of EGCG can be of importance to better utilize it as a chemopreventive and chemotherapeutic agent.