水溶性卟啉及其系列金属化合物的合成、抗癌活性及其作用机制研究

合成了水溶性四-[(4-三甲铵基)苯基]卟啉TAPP及其金属卟啉化合物MTAPP,其中M=Zn(),Cu(),Fe(),Co(),Ni(),Mn().通过元素分析、紫外-可见光谱确定了化合物的组成和结构.以紫外-可见光谱、荧光光谱及粘度法等手段研究了卟啉化合物TAPP和金属卟啉化合物ZnTAPP与小牛胸腺DNA的相互作用,结果表明,TAPP,ZnTAPP与DNA相互作用使紫外-可见光谱发生了8～12nm的红移,并出现了明显的减色效应.荧光光谱强度明显增大,吸收峰位发生变化.以艾氏腹水癌(Ac)和肝癌(Hept)细胞为靶细胞,采用MTT染色法评价了化合物的抗癌活性,部分化合物表现出较高的抗癌活性     

二烃基锡二茂铁羧酸酯的合成及研究

通过二烃基氧化锡与取代二茂铁羧酸缩合，合成14个末见文献报道的二烃基锡 二茂铁羧酸酯化合物．通过对化合物的核磁共振谱、红外光谱、元素分析的研究， 确定化合物的组成和结构及形成结构的原因．化合物12的X衍射单晶测定表明，化 合物是以Sn2O2四元环为中心的中心对称二聚体结构、内环锡为5配位的畸变三角双 锥结构、外环锡为6配位的畸变八面体结构。化合物的抗癌活性实验结果表明，部 分化合物有较高的抗KB肿瘤细胞和抗Bel-7402肿瘤细胞活性．     

meso-5,10,15,20-四（取代2-噻吩基）卟啉及其配合物的合成与表征

用混合溶剂法合成了中位噻吩基取代的卟啉化合物：meso-四(2-噻吩基)卟啉 ，meso-四(4-溴-2-噻吩基)卟啉和meso-四(3-甲基-2-噻吩基)卟啉，产率达到36． 5％-39．3％，考察了溶剂的配比、反应温度、反应时间等因素对反应的影响，其 最佳反应条件为：溶剂配比：丙酸：乙酸：硝基苯：2：2(or3)：1；反应温度： 130~140t；反应时间：50-60min．研究了利用固相合成法合成上述卟啉化合物与过 渡金属盐形成配合物的配位反应，在40℃利用固相合成法合成了卟啉化合物与 Fe2' Fe~3+，CO~2+，Ni~2+，Mn~2+等过渡金属离子形成的配合物，产率为81．1 ％~87．6％．利用元素分析，UV-vis，m，'HNMR， HRMS对卟啉化合物及其配合物 进行了表征，利用TG-DTA研究了它们的热稳定性，利用EPR研究了它们的顺磁性．     

2',3'-双脱氢-2',3'-双脱氧胸苷(d4T)5'-硫代磷酰氨基酸酯的合成和谱学分析

HIV逆转录酶是治疗艾滋病的有效靶点，核苷-磷酰氨基酸酯是HIV逆转录酶的 有效抑制剂，但是这类化合物容易在体内被核酸酶水解。本研究设计合成了对核酸 酶具有抵抗作用的2',3'-双脱氢-2',3'-双脱氧胸苷5'-硫代磷酰氨基酸酯化合物， 这类化合物可以有效地透过细胞膜经过细胞激酶的作用，进入HIV逆转录酶的作用 位点，病毒实验表明该类化合物对MT-4细胞具有较好的抗HIV病毒活性。报道了2', 3'-双脱氢-2',3'-双脱氧胸苷5'-硫代磷酰氨基酸酯化合物的合成，及利用NMR， IR和ESI-MS谱进行的结构表征和构象分析。     

N^2（p—甲基苯磺酰）—L—谷氨酰胺的晶体结构测定

谷氨酰胺衍生物抗瘤酮A_(10)(3-苯乙酰胺基-2,6-哌啶二酮)是从人尿、血液中分离出来的天然广谱性抗肿瘤活性化合物,无明显毒副作用,目前正进行Ⅱ期临床研究.其抗肿瘤的有效成分被认为是它的2个水解产物苯乙酰谷氨酰胶和苯乙酰异谷氨酰胺。De和Pal曾对抗瘤酮A_(10)的类似物如3-对甲苯磺酰胺基-2,6-哌啶二酮等做过抗艾氏腹水癌活性评价,探讨了构效关系.但未见这些化合物的空间结构和电子结构方面的报道.我们合成了抗艾氏腹水癌活性较高的化合物3-对甲苯磷酰胺基-2,6-哌啶二酮的水解产物——对甲苯磺酰谷氨酰胺,并测定了其晶体结构。为进一步研究其分子结构与抗肿瘤活性的关系提供结构数据。     

新型卟啉显色剂-分光光度法测定环保水样中的锌含量

卟啉化合物已作为显色剂用于铜、铁、银、铅、锌等多种金属离子的测定[1-6],效果良好。新型卟啉显色剂——氯化5-[4-N-(对氯)苄铵基吡啶基]-10,15,20-三(4-N-吡啶基)卟啉[7]已应用于水中铜离子的测定[8]。该卟啉试剂同时具有显色和表面活性剂双重功能,水溶性好、抗干扰能力强、灵敏度高。     

meso—四（对—羟基苯基）卟啉与脱氧核糖核酸的作用及其分析应用

报道了非离子型卟啉ｍｅｓｏ－四卟啉与脱氧核糖核酸的作用。在ＰＨ４．９－５．４范围内，ＤＮＡ能与聚合态的ＴＨＰ作用，产生不规则的电子吸收光谱。但如果体系中含有３０％（Ｖ／Ｖ）乙醇，ＤＮＡ与ＴＨＰＰ作用产生４５９．０ｎｍ和７００．０ｎｍ两个新峰。     

一阶导数分光光度法同时测定镀层中的铁和镍

１引言在铁镍合金中添加适量的稀土元素能提高合金的机械性能，使其具有良好的抗蚀性和耐磨性。本文研究了以二甲酚橙为试剂和在适量表面活性剂ＣＴＭＡＢ存在下利用一阶导数分光光度法同时测定铁镍合金镀层中的铁和镍的最佳实验条件，并应用于含有微量稀土元素的铁镍合金镀层中铁和镍含量的同时测定，获得满意的结果。２仪器与试剂美国ＢｅｃｋｍａｎＤＵ－７ＨＳ型分光光度计；ＨＭ－２０Ｅ型ｐＨ计。５０ｍｇ／Ｌ铁标准溶液；５０ｍｇ／Ｌ镍标准溶液；ｐＨ为４．４的ＨＡｃ－ＮａＡｃ缓冲溶液（其中ＮａＡｃ的浓度为０．５ｍｏｌ／Ｌ）；…     

测定N—亚硝基化合物的分光光度法

利用Ｎ－亚硝基化合物的化学去亚硝基反应，建立了一种间接测定Ｎ－亚硝基化合物的分光光度法。实验结果表明，Ｎ－二苯基亚硝胺在０．２￣９．０ｍｇ／Ｌ浓度内呈线性关系。该法应用于香烟烟丝及侧流烟雾萃取液的分析，４次测定ＲＳＤ及回收率分别为１．８６％￣６．３２％，８６．２％￣９６．６％；３．０１％￣５．０３％，１０１．１％￣１０９．１％。     

安替比林基重氮氨基—2,4—二硝基苯间接分光光度法测定痕量氰化物

１引言氰化物是环境监测和食品检验中必测的剧毒物之一。研究表明，在ｐＨ＝１０．５～１２．８的条件下，氰离子使银与安替比林基重氮氨基－２，４－二硝基苯（ＡＰＤＮＢＴ）络合物褪色，其褪色程度与氰离子的浓度呈良好的线性关系，从而建立了新的间接测定氰离子的分光光度方法。对于浓度低于０．０５ｍｇ／Ｌ时氰离子的测定，提出了标准加入分光光度法，提高了低含量氰离子测定的准确度和可靠性。２实验部分２．１仪器和试剂７２２型光栅分光光度计，ｐＨｓ－２型酸度计；银标准溶液为１５．０ｍｇ／Ｌ，氰离子标准溶液为５．０ｍｇ／Ｌ…     

Design,Synthesis, Biological Activity and Molecular Docking Study of Coumarin Derivatives Bearing 2-Methylbiphenyl Moiety

A hybrid pharmacophore approach was used to design and synthesize a series of coumarin derivatives bearing 2-methylbiphenyl moiety, which were evaluated for their in vitro anticancer activities against four cancer cell lines(MCF-75 A549, H460 and HT29) and PD-1/PD-L1 inhibitory activities. Moreover, several compounds with excellent anticancer activities were selected to evaluate the cytotoxicities against one normal cell line(HEK-293). The most promising compound llo showed the best anticancer activities against the four tested cancer cell lines with the IC50 values of 6.45, 8.65, 6,57 and 8.13 gmol/L, respectively, and displayed weak cytotoxicity on the normal cell(HEK-293). Furthermore, screening of PD-1 /PD-L1 inhibitory activity revealed that compound llo could effectively inhibit the binding of PD-1/PD-L1, and the binding interactions of compound llo with PD-L1 protein were explored by molecular docking. All above evidences showed that compound llo might be worthy of further study as a valuable leading compound for the treatment of cancer.     

具有抗癌活性的含磷,锗有机化合物的最新研究进展

对最近几年来所发现的具有抗癌活性的含磷、锗有机化合物的合成及抗癌活性作了综述。     

1,3,4-噻二唑衍生物合成及其生物活性研究进展

1,3,4-噻二唑是含有N、S杂原子的五元杂环化合物,具有多种生物活性。目前,1,3,4-噻二唑及其衍生物广泛用于生物、医药等领域,尤其在抗菌、抗肿瘤、抗癌等方面的研究已取得重大突破。由于1,3,4-噻二唑结构的特殊性以及优越的生物活性,对其进行研究有重要意义。本文主要概述了近年来1,3,4-噻二唑衍生物的几种合成方法以及其在抗菌、抗肿瘤、抗癌方面的研究进展。     

Design and Synthesis of 3-Substituedmethylenethiochroman-4-ones as Anticancer Agents

A series of 3-substituedmethylenethiochroman-4-ones was designed and synthesized, and their structures were confirmed by 1H NMR, 13C NMR, MS, IR, UV and elemental analysis. The results of their anticancer activity studies show that almost all 3-chloromethylenethiochroman-4-ones exhibit high anticancer activities and their activities are all better than reference cisplatin. Their IC50 against cancer cells is in a range of 0.80―9.17 μg/mL. Thus they could be promising candidates for anticancer drugs. However, compound 5 has no activity against cancer cells, thus chloromethylene at the 3 position of thiochroman-4-ones seems to play an important role in observed anticancer activities.     

Oxazinethione Derivatives as a Precursor to Pyrazolone and Pyrimidine Derivatives: Synthesis,Biological Activities,Molecular Modeling,ADME, and Molecular Dynamics Studies

In this study, we used oxazinethione as a perfect precursor to synthesize new pyrimidine and pyrazole derivatives with potent biological activities. Biological activities were determined for all compounds against A. flavus, E. coli, S. aureus, and F. moniliform. Compounds 3, 4a-b, and 5 exhibited higher activities toward A. flavus, E. coli, S. aureus, and F. moniliform; this was indicated through the MIC (minimum inhibitory concentration). At the same time, anticancer activities were determined through four cell lines, Ovcar-3, Hela, MCF-7, and LCC-MMk. The results obtained indicated that compound 5 was the most potent compound for both cell lines. Molecular docking was studied by the MOE (molecular operating environment). The in silico ADME of compounds 2 and 5 showed good pharmacokinetic properties. The present research strengthens the applicability of these compounds as encouraging anticancer and antibacterial drugs. Moreover, JAGUAR module MD simulations were carried out at about 100 ns. In addition, spectroscopic studies were carried out to establish the reactions of the synthesized structure derivatives.     

Folate Functionalized and Evodiamine-Loaded Pluronic Nanomicelles for Augmented Cervical Cancer Cell Killing

Evodiamine (Evo) is a natural, biologically active plant alkaloid with wide range of pharmacological activities. In the present study Evo-loaded folate-conjugated Pluronic F108 nano-micelles (ENM) is synthesized to enhance the therapeutic efficacy of Evo against cervical cancer. ENM are synthesized, physicochemically characterized and in vitro anticancer activity is performed. The study demonstrates that ENM have nanoscale size (50.33 ± 3.09 nm), monodispersity of 0.122 ± 0.072, with high drug encapsulation efficiency (71.30 ± 3.76%) and controlled drug release at the tumor microenvironment. ENM showed dose-dependent and time-dependent cytotoxicity against HeLa human cervical cancer cells. The results of in vitro anticancer studies demonstrated that ENM have significant anticancer effects and greatly induce apoptosis as compared to pure Evo. The cellular uptake study suggests that increased anticancer activity of ENM is due to the improved intracellular delivery of Evo through overexpressed folate receptors. Overall, the designed ENM can be a potential targeted delivery system for hydrophobic anticancer bioactive compound like Evo.     

Current perspectives on quinazolines with potent biological activities: A review

Quinazoline is a heterocyclic compound having biological activities. It is aromatic in nature having bicyclic structure containing benzene ring and pyrimidine ring. Quinazoline and its derivatives are found to have wide range of biological activities that is anticancer, analgesic, antimicrobial, antihypertensive, anticonvulsant, antimalarial, antitumor, and anti-tubercular activities. The purpose of this review is to highlight the recent researches made by researchers on various biological activities of quinazoline derivatives on different targets.     

Tuning the acyclic ether moiety of anticancer agent AA005 with conformationally constrained fragments

A new series of anticancer annonaceous acetogenin mimetics were designed, synthesized, and evaluated based on our previously developed compound AA005, in which a variety of conformationally constrained fragments were introduced. Parallel syntheses of all new compounds were accomplished by replacement of the acyclic bis-ether functionality of AA005 with certain conformationally constrained fragments. Slight effects to the anticancer activity were exerted by altering stereochemistries in the middle modification region. Similar to AA005, most newly synthesized mimetics were found to exhibit potent activities against breast cancer cells, and showed satisfactory selectivities between cancerous and non-cancerous cells. An N,N'-dimethyl bis-amide compound 67 exhibits 30 times more potency against MDA-MB-468 cells than its parent molecule AA005. This study indicates that the introduction of appropriate conformational constraints is a useful optimizing tool for this class of anticancer agents. Successes in the bis-amide analogues of AA005 make this unique class of anticancer agents much simpler and more flexible for future further developments.     

Enhancement of Anticancer Potential of Pterostilbene Derivative by Chalcone Hybridization

Pterostilbene, a natural metabolite of resveratrol, has been indicated as a potent anticancer molecule. Recently, several pterostilbene derivatives have been reported to exhibit better anticancer activities than that of the parent pterostilbene molecule. In the present study, a series of pterostilbene derivatives were designed and synthesized by the hybridization of pterostilbene, chalcone, and cinnamic acid. The cytotoxic effect of these hybrid molecules was determined using two oral cancer cell lines, HSC-3 and OECM-1. (E)-3-(2-((E)-4-Hydroxystyryl)-4,6-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (4d), with IC₅₀ of 16.38 and 18.06 μM against OECM-1 and HSC-3, respectively, was selected for further anticancer mechanism studies. Results indicated that compound 4d effectively inhibited cell proliferation and induced G2/M cell cycle arrest via modulating p21, cyclin B1, and cyclin A2. Compound 4d ultimately induced cell apoptosis by reducing the expression of Bcl-2 and surviving. In addition, cleavage of PARP and caspase-3 were enhanced following the treatment of compound 4d with increased dose. To conclude, a number of pterostilbene derivatives were discovered to possess potent anticancer potentials. Among them, compound 4d was the most active, more active than the parent pterostilbene.     

Semi-Synthesis and In Vitro Anti-Cancer Evaluation of Magnolol Derivatives

Magnolol (MAG), a biphenolic neolignan, has various biological activities including antitumor effects. In this study, 15 MAG derivatives were semi-synthesized and evaluated for their in vitro anticancer activities. From these derivatives, compound 6a exhibited the best cytotoxic activity against four human cancer cell lines, with IC₅₀ values ranging from 20.43 to 28.27 μM. Wound-healing and transwell assays showed that compound 6a significantly inhibited the migration and invasion of MDA-MB-231 cells. In addition, Western blotting experiments, performed using various concentrations of 6a, demonstrated that it downregulates the expression of HIF-1α, MMP-2, and MMP-9 in a concentration-dependent manner. Overall, these results suggest that substituting a benzyl group having F atoms substituted at the C2 position on MAG is a viable strategy for the structural optimization of MAG derivatives as anticancer agents.