蒽醌类亲脂性阳离子的合成及抗癌活性

合成了7个大黄素季铵盐、2个芦荟大黄素季铵盐、1个水溶性大黄素季铵盐和1个α-萘酚醌苯基甲烷季铵盐化合物,并测试了其抗癌活性.含有1条长碳链的大黄素季铵盐的抗癌活性很低,但是含有2条长碳链的大黄素和芦荟大黄素季铵盐的抗癌活性较好.用亲水性的长链替代季铵盐中亲脂性的长碳链会导致大黄素季铵盐失去抗癌活性.α-萘酚醌苯基甲烷季铵盐显示了中等的抗癌活性,表明在具有电子传递能力的分子中引入亲脂性的长碳链季铵盐可以增加其抗癌活性.     

大黄素-香豆素噻唑类衍生物的合成及其抗哈氏弧菌活性

以大黄素为先导化合物，根据活性基团拼接原理，将具有良好抗菌活性的香豆素噻唑和大黄素通过酰胺键连接到同一分子上，设计并合成了6个含有香豆素噻唑的大黄素酰胺类衍生物(8a～8f),并对其抗菌活性进行了评价。结果表明：化合物8b、8c和8f对哈氏弧菌活性存在不同程度的抑制作用，抑菌圈分别为13.37±0.07 mm、 13.60±0.12 mm和13.54±0.09 mm, MIC均为0.25 mg/mL。所有化合物的结构经IR、¹H NMR以及HR-MS(ESI)确证。     

新型含亲水基的噻唑烷-4-酮衍生物的合成及HIV逆转录酶抑制活性

在微波辐射条件下合成了系列C-2或N-3位含酯基的噻唑烷-4-酮衍生物,经水解或还原得到含亲水基如羧基、羟基的衍生物.化合物通过艾滋病毒逆转酶(HIV-RT)试剂盒(比色法)评价了其酶抑制活性.活性结果表明,部分化合物如8a,8b,9a,9b和14c能有效地抑制HIV逆转酶的活性.其中在N-3嘧啶环5位连有乙基的化合物8a和9a的活性最高,IC50值分别为3.02和3.06μmol·L-1.构效关系表明亲水性基团的引入对HIV逆转录酶抑制活性影响不大,而N-3位嘧啶基更有利于噻唑烷-4-酮抗HIV活性.     

二氢噻吩并吡啶-查尔酮衍生物的合成及其体外抗肿瘤活性研究

以2-噻吩乙胺与自制的查尔酮酸进行酰化反应得到酰胺类中间体5a～5j,经Bischer-Napieralski环合反应合成了10个未见报道的二氢噻吩并吡啶-查尔酮衍生物6a～6j,再经去氢反应获得2个噻吩并吡啶-查尔酮衍生物7a和7b.通过噻唑蓝(MTT)法对11种细胞进行体外抗癌活性及安全性测试.结果表明,化合物6a (p-F)、6d (o-Br)和6h (m-OCH3)对HeLa、SGC-7901细胞的抗癌活性优于紫杉醇.当短时间处理(4 h)时, 6j (3,4,5-OCH3)在不影响正常细胞MCF-10A的情况下对癌细胞MCF-7显示强效抗癌效果,值得进一步研究和开发.     

呋喃并呫吨酮衍生物的合成与生物活性研究

以水杨酸、间苯三酚为原料合成了1,3-二羟基呫吨酮, 经醚化、环化反应得到1-羟基呋喃并呫吨酮3a和3b, 再经Mannich反应合成了10个呋喃并呫吨酮衍生物4和5, 接着通过季铵化反应得到相应的10个季铵盐6和7. 运用IR、一维和二维NMR、MS、元素分析等对化合物进行了结构表征, 考察了化合物4～7对乙酰胆碱酯酶的抑制作用及化合物6, 7的抗癌活性. 结果表明: 化合物4～7对乙酰胆碱酯酶具有较好的抑制活性, IC50＝2.0～12.4 μmol/L; 化合物6, 7对肝癌(HepG2)、肺癌(SPC-A)、口腔上皮癌(KB)、乳腺癌(MCF-7)这四种癌细胞株的增殖均有抑制作用, 其中化合物6c对癌细胞株HepG2、化合物7d对癌细胞株MCF-7的抑制作用最强, IC50分别为0.82和0.77 μmol/L.     

单螺环哌嗪季铵盐类化合物的合成及镇痛活性研究

为寻找镇痛活性更好的化合物,以前期发现的螺环哌嗪季铵盐类化合物1为先导物,设计合成了8个未见文献报道的衍生物.通过1H NMR,13C NMR和元素分析或高分辨质谱确定了化合物的结构.利用小鼠醋酸扭体模型初步评价了它们的镇痛活性,构效关系研究表明,苯环上的羟基是关键的药效团,与开链季铵盐相比,螺环季铵盐结构对活性更有利；扩大螺环和引入取代基对活性不利.     

咪唑修饰萘酰亚胺与DNA的作用及其细胞毒性

设计合成了咪唑及其烷基化咪唑阳离子基团修饰的萘酰亚胺衍生物。利用紫外-可见吸收光谱、荧光光谱、圆二色谱和荧光共振能量转移等方法研究了它们与小牛胸腺DNA(CT DNA)和G-四链体DNA的相互作用。这些化合物对端粒DNA序列的G-四链体有很高的结合能力(K_α4×10~6 L·mol~(-1)),并能够稳定G-四链体。DNA粘度实验结果表明萘酰亚胺衍生物与CT DNA通过插入作用结合。Autodock分子对接模拟结果表明这些化合物通过疏水作用、静电作用或氢键等方式与人体端粒G-四链体的loop和沟槽部分结合。咪唑阳离子基团修饰的萘酰亚胺衍生物4a–c能够定位于细胞核,对肺癌细胞的细胞毒性要高于咪唑基团修饰的萘酰亚胺衍生物3。化合物4a和4b对肺癌细胞A549的细胞毒性明显高于正常人胚肺成纤维细胞MRC-5,表现出良好的抗癌活性。     

呫吨酮并吡啶季铵盐的合成及其生物活性

以邻碘苯甲酸和8-羟基喹啉为原料,通过Ullmann反应合成了呫吨酮并吡啶(2),再将其进行季铵化反应合成了它的甲基及乙基季铵盐化合物3a和3b,用IR、NMR、MS及元素分析等测试技术对其结构进行了表征。运用四甲基偶氮唑盐微量酸反应比色法(MTT法)测得化合物3a和3b对体外培养人卵巢癌(A2780)、宫颈癌(Hela)、肺癌(SPC-A)和口腔上皮癌(KB)细胞的抑制作用均优于阳性对照药5-氟尿嘧啶(5-Fu)。溴乙锭置换荧光探针法测得化合物3a和3b与小牛胸腺DNA(CT-DNA)的表观结合常数分别为3.91×105和2.72×105L/mol,揭示目标化合物的抗癌活性可能与其跟DNA的相互作用有关。化合物3a和3b对乙酰胆碱酯酶(AChE)和丁酰胆碱酯酶(BuChE)均具有良好的选择性抑制活性,IC50值达μmol/L以下,与阳性对照药氢溴酸加兰他敏(Galantamine.HBr)近似,它们对AChE的抑制作用为非竞争性抑制。     

新型感绿菁染料的合成

报道了化合物5、季铵盐7和8及三种新型感绿染料(9a、9b、13)的合成方法。对合成的化合物的结构进行了表征。     

新型含取代嘧啶结构的氰基丙烯酸酯类化合物的合成与除草活性研究

为了从氰基丙烯酸酯类衍生物中寻找新的活性化合物,通过活性亚结构拼接方法,设计并合成了一系列未见文献报道的新型含取代嘧啶结构的氰基丙烯酸酯类化合物.其结构均经核磁共振氢谱、碳谱和元素分析确证.初步的生物活性测试结果表明,部分目标化合物显示出较好的除草活性.在1500 g/ha剂量下,化合物9a和9b对芥菜的茎叶处理除草活性分别为90%和100%,化合物9a和9b对繁缕的茎叶处理除草活性分别为90%和100%,化合物9a和9b对小藜的茎叶处理除草效果分别为95%和100%;此外,化合物9b在750 g/ha剂量下对芥菜、繁缕及小藜茎叶处理抑制率均达100%,化合物9b在375 g/ha剂量下对芥菜、繁缕及小藜茎叶处理抑制率分别为90%,80%和90%.     

Synthesis and antibacterial activity of emodin and its derivatives against methicillin-resistant Staphylococcus aureus

Synthesis of the antibacterial emodin was improved using Friedel-Crafts acylation as a key step leading to 37% overall yield. In addition, 21 analogues were synthesized by structural modification of the hydroxyl and methyl groups, as well as the aromatic ring of emodin. Antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and cytotoxicity against noncancerous Vero cells were evaluated. A structure-activity relationship (SAR) study indicated that the hydroxyl groups and the methyl group in the emodin skeleton were crucial for anti-MRSA activity. Furthermore, the presence of an iodine atom or ethylamino group on the aromatic ring enhanced the anti-MRSA activity with higher selectivity indices, while derivatives containing bromine, chlorine atoms or quaternary ammonium salt were as active as emodin. The quaternary ammonium group on the aromatic ring also led to non-cytotoxicity against Vero cells.     

大黄素衍生物的合成及细胞毒性研究

以天然大黄素为母体, 经化学修饰得到一系列新的含氮衍生物6～14. 通过¹H NMR, IR, MS和元素分析确定了结构. 选择口腔底癌(KB)和乳腺癌(MFC-7)两种人癌细胞株, 采用标准MTT法测定了这类大黄素衍生物的细胞毒性. 研究表明大多数衍生物都有较强的抗癌活性, 其中位置异构体7a和7b的混合物表现出最强的活性, 与母体大黄素相比较, 活性分别提高了174倍(KB)和133倍(MFC-7).     

Design,synthesis, cytotoxic activity,and apoptosis inducing effects of 4- and N-substituted benzoyltaurinamide derivatives

In this study, a group of 4-substituted benzoyltaurinamide derivatives were designed, synthesized, and investigated for their anticancer activity against three cancer cell lines and one nontumorigenic cell line by MTT assay. Among the final compounds, methoxyphenyl derivatives 14, 15, 16 were found to be effective against all the tested cancerous cell lines with promising selectivity. The most active compounds were further evaluated to determine the molecular mechanism of their anticancer activity by using western blot assay and the Annexin V-FITC/PI test. Compound 14 (in SH-SY5Y and MDA-MB-231 cell lines) and 15 (in SH-SY5Y cell line) were found to induce intrinsic apoptotic pathway by upregulating BAX, caspase-3, and caspase-9, while downregulating Bcl-2 and Bcl-xL expression levels. According to mechanistic studies, compounds displayed their anticancer activity via three different mechanisms: a. caspase-dependent, b. caspase-independent, and c. caspase-dependent pathway that excluded caspase-9 activation. As a result, this study provides interesting data which can be used to design new taurine-based anticancer derivatives.     

Synthesis and in vitro anticancer activity of some novel tetrahydroquinoline derivatives bearing pyrazol and hydrazide moiety

A new series of tetrahydroquinoline derivatives having pyrazol and hydrazide moieties were synthesized for the purpose of anticancer cell line evaluation. Syntheses of these compounds were firstly achieved by one pot four reactions. The reaction of 3-amino-tetrahydro-1H-pyrazolo [3,4-b]quinolin with aldehydes, indoline-2,3-dione derivatives to give 9a-c , 11a-c , and 13a,b , respectively. In similar manner for biological comparison, the reactions of compound 5 with the same aldehydes and indoline-2,3-dione derivatives to give 19a-c and 20a-c . The newly synthesized compounds were examined in vitro for their cytotoxic activity against HepG-2 and A549 cancer cells. The compounds 11a-c and 20a-c showed promising activity as anticancer agents against HepG-2 and A549 cancer cells.     

Design,synthesis, anticancer activity,and in silico studies of novel imidazo[1,2-a]pyridine based 1H-1,2,3-triazole derivatives

A novel series of imidazo[1,2-a]pyridine based 1H-1,2,3-triazole derivatives were designed, synthesized, and evaluated for their anticancer activity against two different human cancer cell lines. Most of the synthesized compounds displayed anticancer activity with IC₅₀ values from 2.35 to 120.46 μM. Furthermore, compounds 9b , 9c, 9d, 9f , and 9j showed potent inhibitory activity against cancer cell lines, with IC₅₀ values close to that of standard drug. It is important to note that compound 9d was more potent than the standard drug cisplatin with IC₅₀ values of 10.89 and 2.35 μM against Hela cell line and MCF-7 cell line, respectively.     

Design and synthesis of some novel quinoline derivatives as anticancer and radiosensitizing agents targeting VEGFR tyrosine kinase

Quinoline derivatives posses many types of biological activities and have been reported to show significant anticancer activity. There is a variety of mechanisms for the anticancer activity and the most distinguished mechanism is the inhibition of vascular epithelial growth factor receptor tyrosine kinase (VEGFRTK). Novel quinoline derivatives 6 , 7a , 7b , 7c , 8 , 9 , 10 , 11 , 12 and pyrimido[4,5‐b]quinoline derivatives 16 , 17 , 18 , 19 , 20 are reported herein. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7) in which VEGFR is highly expressed. Compounds 6 and 7 with IC₅₀ values of 8.5 μM and 21.9 μM were the most active compounds and exhibited cytotoxic activities higher than that of the reference drug doxorubicin (IC₅₀= 32.02 μM). The most active compounds 6 and 7 were further evaluated for their ability to enhance the cell killing effect of γ‐radiation. J. Heterocyclic Chem., (2011).     

Effect of the concentrations of triphenyltin chloride and anion exchanger on the anion selectivity of a plasticized PVC membrane electrode

 Potentiometric selectivities of a plasticized poly(vinyl chloride) (PVC) membrane containing a hydrophobic quaternary ammonium salt and triphenyltin chloride (TPTCl) for several inorganic anions were evaluated by measurements of the membrane potential of a bi-ionic system (the so-called bi-ionic membrane potential). The addition of TPTCl to the plasticized PVC membrane containing a quaternary ammonium salt gave rise to selectivity patterns different from the Hofmeister anion series, which is observed for a membrane containing only the quaternary ammonium salt. The change in the selectivity pattern from the Hofmeister to the non-Hofmeister was observed under conditions where the TPTCl concentration was higher than the quaternary ammonium salt in the membrane. Response mechanisms and the selectivity of the TPTCl-based electrode are discussed with respect to the concentration dependence of TPTCl and quaternary ammonium salt in the membrane. Received: 6 July 1995/Revised: 2 February 1996/Accepted: 6 February 1996     

Preparation, characterization and application of ZnO sol containing quaternary ammonium salts

The zinc oxide sol containing quaternary ammonium salts (DMDAAC-ZnO) was synthesized by zinc acetate and dimethyldiallyl ammonium chloride via the sol–gel process. Effects of zinc acetate concentration, diethanolamine dosage and dimethyldiallyl ammonium chloride dosage on the absorbance-ratio and viscosity of the sol were investigated. Zinc oxide sols were characterized by XRD, TEM and FT-IR. DMDAAC-ZnO was applied to cotton samples and cotton samples treated were tested by antibacterial activity, UV resistance and breaking strength. The antibacterial activity and UV resistance of samples treated by zinc oxide sol containing quaternary ammonium salt were both better than sample treated by zinc oxide sol.     

Thiazole–Chalcone Hybrids as Prospective Antitubercular and Antiproliferative Agents: Design,Synthesis, Biological,Molecular Docking Studies and In Silico ADME Evaluation

Compounds bearing thiazole and chalcone pharmacophores have been reported to possess excellent antitubercular and anticancer activities. In view of this, we designed, synthesized and characterized a novel series of thiazole–chalcone hybrids (1–20) and further evaluated them for antitubercular and antiproliferative activities by employing standard protocols. Among the twenty compounds, chalcones 12 and 7, containing 2,4-difluorophenyl and 2,4-dichlorophenyl groups, showed potential antitubercular activity higher than the standard pyrazinamide (MIC = 25.34 µM) with MICs of 2.43 and 4.41 µM, respectively. Chalcone 20 containing heteroaryl 2-thiazolyl moiety exhibited promising antiproliferative activity against the prostate cancer cell line (DU-145), higher than the standard methotrexate (IC₅₀ = 11 ± 1 µM) with an IC₅₀ value of 6.86 ± 1 µM. Furthermore, cytotoxicity studies of these compounds against normal human liver cell lines (L02) revealed that the target molecules were comparatively less selective against L02. Additional computational studies using AutoDock predicted the key binding interactions responsible for the activity and the SwissADME tool computed the in silico drug likeliness properties. The lead compounds generated through this study, create a way for the optimization and development of novel drugs against tuberculosis infections and prostate cancer.     

Dependence of the anticancer activity of 1,3‐oxazole derivatives on the donor/acceptor nature of his substitues

A series of new 1,3‐oxazole derivatives, containing in position 5 both donor and acceptor substituents were synthesized. These substances were considered as potentially active anticancer pharmacophores in the human tumor cell line panel derived from nine cancer types, including lung, colon, melanoma, renal, ovarian, brain, leukemia, breast, and prostate. Primary in vitro one‐dose anticancer screening was shown that compounds with acceptor substituents (such as –C(O)OMe, –CN) in the position 5 inhibit the growth of most cell lines, and compounds with donor substituents (such as –NHR, ?SR) in the position 5 do not practically inhibit the growth of cancer cell lines. It can be assumed that the pharmacological activity of 1,3‐oxazole derivatives depends on donor/acceptor nature of the substituents in position 5. It was proposed to evaluate the donor/acceptor ability of 1,3‐oxazole derivatives using the special parameter φ₀, which takes into account the relative position of the boundary levels (HOMO end LUMO). The quantum‐chemical modeling was performed; the special parameter φ₀ for 1,3‐oxazole derivatives correlates with the experimental results. Quantum‐chemical calculations of the special parameter φ₀ allow modeling the pharmacological activity of 1,3‐oxazole derivatives by introducing donor or acceptor substituents at position 2 or 5. This work may be useful for chemists to develop a target synthesis of potential biologically active compounds.