An Improved Synthesis of Tn Antigen

Tn (GalNAc(1?O-Ser/Thr) 6 is a human tumor-associated carbohydrate antigen1. Protein conjugates of Tn antigen have a role for the active specific immunotherapy of cancer. The total synthesis of Tn antigen has been reported2 by glycosidating between 3,4,6-tri-O-acetyl-2-azido-2-deoxy-(-D-galactopyranosyl chloride and L-serine derivative, then removing the protecting groups. In this route, the key intermediate 3,4,6-tri-O-acetyl-2-azido-2-deoxy-(-D-galactopyranosyl chloride was afforded by …     

1,2-苯并噻嗪类化合物的设计、合成及抗肿瘤活性研究

依据生物电子等排原理,设计合成了13个全新结构的1,2-苯并噻嗪类化合物,其结构均经IR,1H NMR,13C NMR和MS确证.以A431,A549,MDA-MB-468和HL60 4种细胞株为活性筛选对象,采用四甲基偶氮唑盐(MTT)法进行初步的体外抗肿瘤活性研究.结果表明,部分化合物对肿瘤细胞有一定的抑制活性,其中化合物5b对A431具有显著的抑制活性,IC50值为1.57μmol/L,化合物9a对A431,A549和MDA-MB-468 3种细胞株的抑制活性均强于阳性对照药gefitinib.并采用Moe软件对所合成的化合物与表皮生长因子受体(EGFR)结合位点进行对接,以进一步阐释所合成化合物的作用靶标.     

Synthesis and Biological Activity Screening of Newly Synthesized Trimethoxyphenyl-Based Analogues as Potential Anticancer Agents

A group of novel trimethoxyphenyl (TMP)-based analogues were synthesized by varying the azalactone ring of 2-(3,4-dimethoxyphenyl)-4-(3,4,5-trimethoxybenzylidene)oxazolone 1 and characterized using NMR spectral data as well as elemental microanalyses. All synthesized compounds were screened for their cytotoxic activity utilizing the hepatocellular carcinoma (HepG2) cell line. Compounds 9, 10 and 11 exhibited good cytotoxic potency with IC₅₀ values ranging from 1.38 to 3.21 μM compared to podophyllotoxin (podo) as a reference compound. In addition, compounds 9, 10 and 11 exhibited potent inhibition of β-tubulin polymerization. DNA flow cytometry analysis of compound 9 shows cell cycle disturbance at the G2/M phase and a significant increase in Annexin-V-positive cells compared with the untreated control. Compound 9 was further studied regarding its apoptotic potential in HepG2 cells; it decreased the level of MMP and Bcl-2 as well as boosted the level of p53 and Bax compared with the control HepG2 cells.     

New Pyridopyrimidone Derivatives: Synthesis,Molecular Docking Studies,and Potential Anticancer Activity

Russian Journal of General Chemistry - A new series of pyrido[2,3-d]pyrimidones incorporated pyrazoles and fused triazoles are synthesized and tested in vitro for cytotoxic effect against cancer...     

Synthesis and Anticancer Activity of Podophyllotoxin Derivatives

Chemistry of Natural Compounds - Two series of podophyllotoxin derivatives were synthesized by addition of a 4β-sulfanilamide to or substitution of a 4β-amide into podophyllotoxin. Their...     

缩胺硫脲化合物的合成及其抗癌活性的研究

以肼基二硫代甲酸甲酯(Ⅱ)与相应的酮或醛反应,生成3-二取代甲撑基二硫代甲酸甲酯(Ⅲ).化合物与N-单取代哌嗪反应,制得不同取代基的标题化合物缩胺硫脲(Ⅰ),产率27～85.产物的结构用IR,NMR和元素分析证实,用磺酰罗丹明β蛋白染色法(SRB法)和四氮唑盐还原法(MTT法)检验了它们对鼠白血病(P-388)和人肺癌(A-549)细胞株的抑制活性.     

Synthesis and Anticancer Activity of Certain Selenophene Derivatives

Russian Journal of Organic Chemistry - Selenopheno[2,3-d]pyrimidine- and selenopheno[2,3-d][1,2,3]triazine-containing compounds were synthesized starting from...     

Synthesis and Anticancer Activity of New Substituted Pyrazoles and Their Derived 1,2,4‐Triazoles and Sugar Derivatives

New substituted pyrazole, thiazole, and 1,2,4‐triazole derivatives were synthesized. The sugar hydrazones, their acetylated derivatives as well as their derived acyclic C‐nucleoside analogs, and the thioglycosides of the 1,2,4‐traizole derivatives were also prepared. The antitumor activity of some of the synthesized compounds were studied, and a number of the tested compounds showed significant activities.     

嘧啶联苯类化合物的设计、合成及抗肿瘤活性

设计合成了一系列以嘧啶联苯为中心结构的潜在激酶变构抑制剂.以2,4-二氯-5-甲基嘧啶为起始原料,通过Suzuki偶联一锅法合成了中心药效团嘧啶联苯,通过X射线单晶衍射分析确认结构,并在此基础上衍生化合成了19个化合物.采用噻唑蓝(MTT)法对所得化合物用人乳腺癌细胞(MCF-7)进行体外抗肿瘤活性初步筛选,并找到2个具有潜在应用价值的化合物8c(IC50=0.224μmol/L)和9c(IC50=0.113μmol/L).     

大黄素衍生物的合成及抗癌活性

通过对大黄素的C6位进行化学修饰, 设计合成了7个含氮杂环的大黄素衍生物和3个含季铵盐基团的大黄素衍生物. 通过红外光谱、 ¹H NMR和质谱表征了所制备化合物的结构, 并测试了它们对白血病细胞Molt-4和淋巴瘤细胞CA46的体外抑制活性. 其中化合物8, 9a+9b, 20a, 20b和20c均显示出比大黄素更高的抗癌活性, 表明苯并咪唑基团和季铵盐基团是大黄素提高抗癌活性的有效药效团.     

A Review on Mechanistic Insight of Plant Derived Anticancer Bioactive Phytocompounds and Their Structure Activity Relationship

Cancer is a disorder that rigorously affects the human population worldwide. There is a steady demand for new remedies to both treat and prevent this life-threatening sickness due to toxicities, drug resistance and therapeutic failures in current conventional therapies. Researchers around the world are drawing their attention towards compounds of natural origin. For decades, human beings have been using the flora of the world as a source of cancer chemotherapeutic agents. Currently, clinically approved anticancer compounds are vincristine, vinblastine, taxanes, and podophyllotoxin, all of which come from natural sources. With the triumph of these compounds that have been developed into staple drug products for most cancer therapies, new technologies are now appearing to search for novel biomolecules with anticancer activities. Ellipticine, camptothecin, combretastatin, curcumin, homoharringtonine and others are plant derived bioactive phytocompounds with potential anticancer properties. Researchers have improved the field further through the use of advanced analytical chemistry and computational tools of analysis. The investigation of new strategies for administration such as nanotechnology may enable the development of the phytocompounds as drug products. These technologies have enhanced the anticancer potential of plant-derived drugs with the aim of site-directed drug delivery, enhanced bioavailability, and reduced toxicity. This review discusses mechanistic insights into anticancer compounds of natural origins and their structural activity relationships that make them targets for anticancer treatments.     

一种具有抗肿瘤活性胆酸衍生物的合成新方法

以胆酸为原料, 使之与甲醇反应, 得到胆酸甲酯(2). 2采用PCC(氯铬酸吡啶)氧化得到脱氢胆酸甲酯(3), 3在CoCl2存在的条件下通过NaBH4的化学选择性还原得到7α-羟基-3,12-二氧代胆酸甲酯(4). 对4的抗肿瘤活性试验表明该化合物对Sk-Hep-1(肝癌)和H-292(肺癌)细胞株具有中等程度的细胞毒性.     

Synthesis and Anticancer Activity of Oxadiazole Incorporated Ellipticine Derivatives

Russian Journal of General Chemistry - A series of ellipticine derivatives 8a–8j containing oxadiazole structural block are synthesized and evaluated for their anticancer activity on human...     

Synthesis of New Thiazole-Pyridine Hybrids and Their Anticancer Activity

Russian Journal of General Chemistry - A series of new thiazole incorporated pyridine derivatives containing the phenoxyacetamide moiety as a linking bridge has been synthesized. The synthetic...     

Novel 4-Azapregnene Derivatives as Potential Anticancer Agents: Synthesis,Antiproliferative Activity and Molecular Docking Studies

A series of novel 21E-arylidene-4-azapregn-5-ene steroids has been successfully designed, synthesized and structurally characterized, and their antiproliferative activity was evaluated in four different cell lines. Within this group, the 21E-(pyridin-3-yl)methylidene derivative exhibited significant cytotoxic activity in hormone-dependent cells LNCaP (IC₅₀ = 10.20 µM) and T47-D cells (IC₅₀ = 1.33 µM). In PC-3 androgen-independent cells, the steroid 21E-p-nitrophenylidene-4-azapregn-5-ene was the most potent of this series (IC₅₀ = 3.29 µM). Considering these results, the 21E-(pyridin-3-yl)methylidene derivative was chosen for further biological studies on T47-D and LNCaP cells, and it was shown that this azasteroid seems to lead T47-D cells to apoptotic death. Finally, molecular docking studies were performed to explore the affinity of these 4-azapregnene derivatives to several steroid targets, namely 5α-reductase type 2, estrogen receptor α, androgen receptor and CYP17A1. In general, compounds presented higher affinity to 5α-reductase type 2 and estrogen receptor α.     

Novel Furochromone Derivatives: Synthesis and Anticancer Activity Studies

Medicinal plant extracts have been used for medical purposes throughout human history. In this study, khellin, having furochromone structure, which is obtained from a well‐known traditional medicinal plant, was selected. A series of furochromonyl compounds ( K1 – K14 ) were synthesized for their anticancer activities. Furochromonyl compounds ( K1 – K14 ) were synthesized by Knoevenagel reaction of substituted 2,4‐thiazolidinediones ( Ia – j )/rhodanines ( Ik – n ) with khellin‐2‐carboxaldehyde ( V ), and their cytotoxicity was investigated in 22 cancer cell lines, which were originated from tissues such as the liver, breast, colon, and cervix. As the first step, two hepatocellular carcinoma cell lines Huh7 and PLC/PRF/5 (Alexander cells) were treated with 10 μM of each compound for 72 h, and then sulforhodamine B assay was performed to analyze their anti‐growth activities. Ethyl 2‐(5‐((4,9‐dimethoxy‐5‐oxo‐5H‐furo[3,2‐g]chromen‐7‐yl)methylene)‐4‐oxo‐2‐thioxothiazolidin‐3‐yl)acetate ( K11 ) was found as the most cytotoxic compound of primary screening. Afterwards, 12 hepatocellular carcinoma, seven breast cancer, two colon cancer, and a cervical cancer cell lines were selected to test K11 for 72 h at multiple concentrations to determine 50% effective doses. Results showed that the 14 cell lines were affected by K11 quantities lower than 10 μM. The structure of K11 , which is particularly effective on breast cancers, can be used to slow down the progression of tumors. Furthermore, the discovery of more effective compounds can be carried out on the basis of this structure.     

水合三环己基锡4-吡啶甲酸酯配合物的合成、结构及抗癌活性

三环己基氢氧化锡与4-吡啶甲酸按物质的量比1∶1在乙醇溶剂中反应,合成了水合三环己基锡4-吡啶甲酸酯配合物。采用元素分析、红外光谱、核磁共振、差热分析和X-射线单晶衍射等对配合物进行了结构表征,并对配合物进行量子化学计算和体外抗癌活性研究。结果表明：配合物中心锡原子为五配位畸变三角双锥构型;配合物对人肝癌细胞(HUH7)、人肺腺癌细胞(A549)、人表皮癌细胞(A431)和人结肠癌细胞(HCT-116)的抑制活性高于顺铂。     

A Greener Approach Synthesis and Docking Studies of Perimidine Derivatives as Potential Anticancer Agents

Microwave solvent‐free technique was employed to the synthesis of series of 2‐(1H‐perimidin‐2(3H)‐ylidene) derivatives, 4‐(1H‐perimidin‐2‐yl)‐1H‐pyrazole‐3‐carboxamides, pyrrolo[1,2‐a]perimidin‐10‐ones, and 8H‐[1,2,4]triazolo[4,3‐a]perimidine. Compared with conventional method, the obvious feature of microwave method is higher in chemical yield, faster reaction rate, and cleaner reaction condition. The structures of the synthesized compounds were confirmed based on their elemental analyses and spectroscopic data (FT‐IR, ¹H‐NMR, ¹⁹F‐NMR, ¹³C‐NMR, and LC‐MS/MS). Some of the synthesized compounds exhibit anticancer potential against the growth of both the human breast (MCF‐7) and the liver carcinoma (HepG2) tumor cells. The most active cytotoxic perimidine derivatives were docked against topoisomerase II to investigate their binding and DNA intercalating activity against the protein crystal structure.     

Synthesis and Anticancer Activity of 1,2,3-Triazole Fused N-Arylpyrazole Derivatives

A novel series of triazole derivatives 11a–11j is synthesized. Structures of the products are confirmed by ¹H and ¹³C NMR, and mass spectral data. The anticancer activities of compounds 11a–11j are evaluated against three human cancer cell lines (MCF-7, A549, and A375) using the standard MTT assay in vitro, using doxorubicin as the positive control. All the compounds exhibit significant activity against cancer cell lines. The compounds 11a, 11d, 11e, 11g, and 11j demonstrate more potent activity than the positive control.