Design, synthesis and antitumor activity of a series of novel coumarin-stilbene hybrids, the 3-arylcoumarins

A series of novel coumarin-stilbene hybrids called 3-arylcoumarins were synthesized via Perkin reaction and evaluated as potential antitumor agents. The results showed that some compounds exhibited in vitro activity against KB, KV, MCF-7, MCF-7/ADR cell lines to some extent. Compound 3a showed remarkable effect against KB tumor cells with an IC50 value of 5.18 μmol/L.     

新型3-芳基香豆素类化合物的合成及其抗肿瘤活性

以芳基乙酸和取代邻羟基苯甲醛为起始原料,经Perkin缩合和关环反应合成了16个新型的3-芳基香豆素类化合物(3a~4h),其结构经1H NMR,IR和EI-MS表征。采用MTT法测定了3和4对人鼻咽癌细胞株(KB)、人气道平滑肌细胞株(KV)、人乳腺癌细胞株(MCF-7)、人乳腺癌多药耐药细胞株(MCF-7/ADR)的细胞毒性。结果表明:部分化合物表现出较强的细胞增殖抑制活性,其中7,8-二乙酰氧基-3-(4'-甲氧基苯基)香豆素(3e)对KB细胞的活性最强(IC505.88μmol·L-1)。     

放线菌素D新类似物的设计、合成与体外抗肿瘤活性

为了提高临床抗肿瘤药物放线菌素D(AMD)的抗肿瘤效果和治疗指数,在AMD构效关系研究基础上,设计全合成了包括9个新类似物在内的两类共13个AMD类似物.保持环肽2位D-Val不变,环肽5位分别用Sar,D-Me-Leu和Me-Ile等氨基酸替换以改变侧链基团长度,合成了类似物8b～8e;以环肽2位D-Phe替换的低毒性类似物[D-Phe2]2AMD为基础,在环肽5位进行氨基酸替换,改变侧链基团长度和空间指向,并引入芳香族氨基酸等,合成了类似物8f～8m.优化了类似物的合成中的反应条件,提高了五肽环化产率,避免了消旋产物的生成.所有类似物经[α]D,1HNMR和高分辨质谱表征后,采用MTT法进行了体外抗肿瘤活性筛选,结果表明,保留环肽2位D-Val及延长5位氨基酸侧链基团能显著提高类似物的抗肿瘤活性,而2位D-Phe替换后类似物的抗肿瘤活性普遍下降.     

Synthesis and Antitumor Activity of Capecitabine Derivatives

A series of capecitabine derivatives with a Boc group at the N⁴-position was synthesized and their in vitro antitumor activities against HepG2(liver hepatocellular carcinoma) were primarily evaluated. Some compounds were chosen for further evaluation of their in vivo efficacy on nude mice xenografted human hepatoma HepG2. The results showed that compounds 3 and 6 had considerable in vivo activity against HepG2, with tumor growth inhibition rates of 70% and 64% on day 21, respectively, and 56% and 55% on day 35, respectively, which are roughly comparable to capecitabine(74% and 59% on days 21 and 35, respectively).     

抗癌性吲哚喹唑啉衍生物3D-QSAR研究及其分子设计

吲哚喹唑啉衍生物是近年来发现的一类具有良好抗癌活性的化合物. 作者在最近报道的二维定量构效关系(2D-QSAR)的基础上, 采用比较分子力场方法(CoMFA)进一步对该系列化合物进行三维定量构效关系(3D-QSAR)研究, 建立了3D-QSAR的CoMFA模型, 其非交叉验证相关系数r2=0.986, 标准偏差SD=0.084, 统计方差比F=114.6, 交叉验证相关系数q2=0.695, 表明该模型合理、可信, 并具有良好的预测能力. 研究结果表明: (1) 取代基R1的部位上静电效应起主要作用, 并且确保取代基R1的第一个原子具有较大的净正电荷, 对提高化合物的抗癌活性十分重要. 这与2D-QSAR研究结果相一致. (2) 取代基R2的部位上立体效应起主要作用, R2的体积大小要适中. 应用这些规律进行了分子设计, 在理论上获得了一些具有较高抗癌活性的新的吲哚喹唑啉衍生物, 并期待实验证实. 该QSAR的研究结果可为实验工作者合成新药提供理论参考.     

Design,Synthesis and Antitumor Activity of Fluoroquinolone C3 Heterocyclic Bis-oxadiazole Methylsulfide Derivatives Derived from Levofloxacin

To discover an efficient route for the shift from an antibacterial fluoroquinolone to an antitumor one based on the mechanistic similarities between targeting topoisomerases and the eukaryotic ones, two series of the title compounds, C3 bis-oxadiazole methylsulfides 6a-6h and corresponding dimethylpiperazinium iodides 7a-7h derived from levofloxacin 1 were designed and synthesized. Their in vitro antiproliferative activities against Chinese hamster ovary cell line(CHO), murine leukemia cell line(L1210) and human leukocytoma cell line(HL60) were evaluated by MTT assay, and inhibitory effect on DNA topoisomerase IIα was also measured by means of densitometric assay.     

二肽类膦酸酯衍生物的合成与抗肿瘤活性

为了寻找抗肿瘤活性化合物,以前期研究的含一个氨基酸结构单元的膦酸酯衍生物为基础,设计合成了15个二肽类膦酸酯衍生物(Ⅲa-Ⅲo).采用溴化噻唑蓝四氮唑(MTT)法进行体外抗肿瘤活性测试.结果表明:该类化合物对人肺癌细胞(A-549)、人胃癌细胞(SGC-7901))和人食管癌细胞(EC-109)有潜在增殖抑制作用.其中...     

Design,Synthesis and Antitumor Activity of Pyrrolopyrazinone-chalcone Hybrids

A series of pyrrolopyrazinone-chalcone hybrids（12a-12q） was designed,synthesized and screened for their antitumor activity against SKOV-3,A549 and HeLa cell lines in vitro.Compared with the pyrrolopyrazinone（10a） and 5-fluorouracil（5-FU）,nearly all the tested compounds showed significantly-improved antitumor activities.The most promising compounds 12e and 12k（IC50=0.25 and 0.88 μmol/L） respectively show activities of 123and 35 times that of compound 10a（IC50=30.74 μmol/L） against HeLa cell line.The result reveals that the presence of chalcone moiety is beneficial to their activity and selectivity.     

3-芳基苯并呋喃酮类化合物的合成及抗肿瘤活性

以甲氧基取代苯甲醛和氯仿为起始物, 以四丁基溴化铵(TBAB)为催化剂, 在氢氧化钠溶液中反应制得甲氧基取代扁桃酸钠, 经酸化得到相应的甲氧基取代扁桃酸; 在三氟化硼-乙醚催化下, 甲氧基取代扁桃酸分别与不同的酚类化合物发生串联的酯化-分子内环合反应, 便捷、 高效地合成了13种3-芳基苯并呋喃酮类化合物. 采用噻唑蓝(MTT)法对其中11种化合物进行了肿瘤细胞增殖抑制活性研究, 结果表明化合物4a, 4j及4a, 4i具有较强的抗肿瘤活性.     

Design,Synthesis and Antitumor Activity of a Novel Series of PAC-1 Analogues

A novel series of first procaspase activating compound(PAC-1) analogues was designed, synthesized and evaluated for antitumor activity towards two cell lines[human promyelocytic leukemia cell line(HL60) and human embryonic lung fibroblast cell line(HLF)] by the MTT[3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazo-liumromide] method in vitro. The structures of all the compounds were confirmed by ¹H NMR, MS and elemental analysis. Among the compounds synthesized,(E)-2-[(3-{[4-(tert-butyl)benzyl](methyl)amino}propyl)(methyl)amino]-N'-[4-(diethylamino)-2-hydroxybenzylidene]acetohydrazide(compound 6n) exhibits a good anti-proliferative activity to the majority of tumor cells tested, and selectively cleaves cancer cells. Thus, compound 6n was identified as promising lead compound for further structural modification.     

Synthesis and Antitumor Activity of Sorafenib Analogs Containing a Tetrazole Moiety

A novel series of diaryl biuret derivatives containing a tetrazole moiety was designed and synthesized.All the target compounds were evaluated for their in vitro antitumor activity against HT-29,HepG2,MCF-7 and A549 cells by MTT assay.Most of them exhibited obvious antitumor activity,and four of them(4a,4c,4h and 7a)were superior to sorafenib in general.Among them,Compound 4h displayed more potent activity than sorafenib in all tested cancer cells.Compound 4c exhibited the most outstanding activity in inhibition of growth of HepG2 cells(IC50=0.55 μmol/L).Further,they both revealed favorable metabolic stability in in vitro assay.Compounds 4c and 4h are promising candidates for further development.     

含己烷雌酚的聚磷酸酯的合成及其抗肿瘤活性研究

合成了３种主链含己烷雌酚的生物可降解的聚磷酸酯，结构经ＩＲ，＾１ＨＮＭＲ和元素分析鉴定，通过水接触角的测定研究了聚合物的亲水－疏水性能，以ｐＨ值变化表征了聚合物的体外水解速率。初步的体外实验表明，此类聚磷酸酯具有较好的体外抗艾氏腹水癌活性。     

Synthesis and Antitumor Activity of 7-Substituted Derivatives of Homocamptothecin

Camptotecin is the parent of an important class of anticancer agents which, can selectively poison the ubiquitous nuclear enzyme topoisomerase. Water soluble camptothecin analogues such as topotecan and irinotecan are already approved for clinical uses in…     

Synthesis,Antitumor Activity and Preliminary Structure-activity Relationship of 2-Aminothiazole Derivatives

In this paper, we described the synthesis of 2-aminothiazole sublibrary containing methyl, bromo, phenyl or butylidene at 4- or/and 5-position of its core. All target compounds were evaluated for their antitumor activities against human lung cancer cell line H1299 and human glioma cell line SHG-44. Among the compounds screened, 4,5,6,7-tetrahydrobenzo[d]thiazole(26b) exhibited the most potent antitumor activities with IC₅₀ values of 4.89 and 4.03 μmol/L against the two tested cell lines, respectively. Preliminary structure-activity relationship(SAR) studies of these compound were subsequently investigated.     

金诺芬衍生物的合成及抗肿瘤活性

设计合成了一类新型金诺芬衍生物, 采用核磁共振波谱(NMR)和高分辨质谱(HRMS)确认了其结构. 以目标化合物处理肿瘤细胞后, 采用四氮唑蓝盐(MTS)法检测细胞增殖情况, 用流式细胞仪检测细胞凋亡情况, 采用蛋白质免疫印迹(Western blot)法检测总的泛素化蛋白(Ub-Prs)、 K48 位链接多聚泛素化蛋白以及蛋白酶体外源性特异性底物(GFPu)的表达情况. 结果表明, 金诺芬衍生物可通过抑制蛋白酶体功能来发挥抗肿瘤效果.     

Synthesis and Antitumor Activity of 4-tert-Butyl-5-benzyl-2-benzyliminothiazoles

A series of novel Schiff bases including 4-tert-butyl-5-benzyl-2-benzyliminothiazoles was synthesized by reacting the aromatic aldehydes with the corresponding 2-aminothiazoles.The antitumor bioassay revealed that compounds 2n and 2m exhibited potent cytotoxicity against human cervix cancer（HeLa） cell line with IC50 values of 0.001 and 0.007 mmol/L,respectively.The preliminary structure-activity relationship（SAR） investigations and the apoptosis evaluation suggest that 4-tert-butyl-5-benzyl-2-benzyliminothiazoles may be a satisfactory backbone for antitumor activity,and compound 2n can serve as an attractive candidate for the development of novel apoptosis in anticancer treatment.     

饶丹宁甲叉基取代左氧氟沙星衍生物的合成与抗肿瘤活性

为寻找提高氟喹诺酮肿瘤活的有效结构修饰策略,左氧氟沙星(3)的衍生物(S)-(-)-9-氟-2,3-二氢-3-甲基-10-(4-甲基-1-哌嗪基)-[1,4]噁嗪并[2,3,4-ij]-喹啉-7(4H)-酮-6-甲醛(5)与饶丹宁类(2a-2l)通过Claisen-Schmid缩合反应构建了饶丹宁甲叉基取代左氧氟沙星衍...     

1-(3-芳亚甲基氨基)丙基-2,8,9-三氧杂-5-氮杂-1-硅杂双环[3,3,3]十一烷金属络合物的合成及其抗肿瘤活性研究

我们曾对1-亚甲基氨基烷基-2,8,9-三氧杂-5-氮杂-1-硅杂双环[3,3,3]十一烷的合成及其抗肿瘤活性作过研究,发现1-[3-(2-羟基苯亚甲基氨基)丙基]-2,8,9-三氧杂-5-氮杂-1-硅杂双环[3,3,3]十一烷和1-[3-(2,4-二羟基苯亚甲基氨基)丙基]-2,8,9-三氧杂-5-氮杂-1-硅杂双环[3,3,3]十一烷具有较好的抗肿瘤活性。已知亚甲胺类(Schiff碱)化合物与某些金属离子形成络合物后,能提高它们的抗肿瘤活性。为此,我们进一步研究了这两种亚甲胺衍生物的合成及其抗肿瘤活性。     

Design,Synthesis, Inhibiting HDACs Ability and Antitumor Activity of Pyrimidin-4(3H)-one Hydroxamate Derivatives

A series of novel pyrimidin-4(3H)-one hydroxamate derivatives was designed, synthesized and studied for their activities against histone deacetylases(HDACs). The results indicate that all the compounds show HDACs inhibitiory activity. The antiproliferative activities of the compounds against HeLa and A549 cells were also investigated. The pharmacological results show compound 9g has potent activity in the enzymatic inhibition assay and cell-based assay.     

短肽5－氟尿嘧啶前体药物的合成及其抗肿瘤活性研究

短肽５－氟尿嘧啶前体药物的合成及其抗肿瘤活性研究罗毅,卓仁禧,范昌烈（武汉大学化学系,武汉,４３００７２）关键词氨基酸,短肽,５－氟尿嘧啶,抗肿瘤活性５－氟尿嘧啶（５－ＦＵ）是一种治疗癌症的广谱性抗代谢药物,但由于其毒副作用较大,从而限制了它在临床上...