Mitochondrial Fragmentation Is an Important Cellular Event Induced by Ruthenium(II) Polypyridyl Complexes in Osteosarcoma Cells

A series of ruthenium(II) polypyridyl complexes were synthesized and evaluated for their in vitro anticancer activities. The results showed that ruthenium polypyridyl complexes, especially [Ru(bpy)₂(p‐tFPIP)]²⁺ ( 2 a ; bpy=bipyridine, tFPIP=2‐(2‐trifluoromethane phenyl)imidazole[4,5‐f][1,10]phenanthroline), exhibited novel anticancer activity against human cancer cell lines, but with less toxicity to a human normal cell line. The results of flow cytometry and caspase activities analysis indicated that the 2 a ‐induced growth inhibition against MG‐63 osteosarcoma cells was mainly caused by mitochondria‐mediated apoptosis. DNA fragmentation and nuclear condensation as detected by TUNEL–DAPI co‐staining further confirmed 2 a ‐induced apoptotic cell death. Further, fluorescence imaging revealed that ruthenium(II) polypyridyl complexes could target mitochondria to induce mitochondrial fragmentation, accompanied by depletion of mitochondrial membrane potential. Taken together, these findings suggest a potential application of theses ruthenium(II) complexes in the treatment of cancers.     

Three platinum(II) complexes of 2-(methoxy-phenyl)-imidazo-[4,5-f]-[1,10] phenanthroline: cell apoptosis induction by sub-G1 phase cell cycle arrest and G-quadruplex binding properties

Three platinum(II) complexes, including 2-(2-methoxy-phenyl) imidazo [4,5-f]-[1,10] phenanthroline, 2-(3-methoxy-phenyl) imidazo [4,5-f]-[1,10] phenanthroline and 2-(4-methoxy-phenyl) imidazo [4,5-f]-[1,10] phenanthroline, were synthesised and structurally characterised. In complexes 1–3, the platinum centre adopts a four-coordinate square planar geometry. In the MTT assay, these complexes exhibited considerable cytotoxicities against the SPC-A-2, MGC80-3, BEL-7404 and HeLa human tumour cell lines, with IC₅₀ values in the range of 4.7 ± 0.8 to 23.3 ± 0.4 μM, and lower cytotoxicities towards the HL-7702 human normal liver cell line. By flow cytometry analyses, the HeLa cells treated with complexes 1–3 for 72 h exhibited DNA damage at the sub-G1 phase with a dose-dependent effect resulting in the blockage of cell cycle at sub-G1 phase, which might contribute to the cell apoptosis observed in HeLa cells. From the results of the CD, UV–vis and FID spectral analyses, complexes 1–3 showed good binding affinity with human telomeric G-quadruplex DNA. It suggested the potential inhibition on the telomerase activity, which should be a key antitumour mechanism for complexes 1–3. Furthermore, complex 1 with 2-substituted MOIP ligand, which may have lower steric hindrance for DNA intercalation, showed higher G-quadruplex DNA binding affinity than complexes 2 and 3. This was supported by the results from cell growth inhibition and cell apoptosis induction.     

A Series of New Ligustrazine-Triterpenes Derivatives as Anti-Tumor Agents: Design,Synthesis, and Biological Evaluation

A series of novel ligustrazine-triterpenes derivatives was designed, synthesized and screened for their cytotoxicity against five cancer cell lines (Bel-7402, HepG2, HT-29, Hela, and MCF-7) and Madin-Darby canine kidney (MDCK). Current study suggested that most of the ligustrazine-triterpenes conjunctions showed better cytotoxicity than the starting materials. In particular, compound 4a exhibited better cytotoxic activity (IC₅₀ < 5.23 μM) against Bel-7402, HT-29, MCF-7, Hela, and HepG2 than the standard anticancer drug cisplatin (DDP). The cytotoxicity selectivity detection revealed that 4a exhibited low cytotoxicity (IC₅₀ > 20 μM) towards MDCK cells. A combination of fluorescence staining observation and flow cytometric analysis indicated that 4a could induce HepG2 cell apoptosis. Further studies suggested that 4a-induced apoptosis is mediated through depolarization of the mitochondrial membrane potential and increase of intracellular free Ca²⁺ concentration. In addition, the structure-activity relationships of these derivatives were briefly discussed.     

TM4SF1 Promotes Proliferation,Invasion, and Metastasis in Human Liver Cancer Cells

Transmembrane 4 superfamily member 1 (TM4SF1) is a member of tetraspanin family, which mediates signal transduction events regulating cell development, activation, growth and motility. Our previous studies showed that TM4SF1 is highly expressed in liver cancer. HepG2 cells were transfected with TM4SFl siRNA and TM4SF1-expressing plasmids and their biological functions were analyzed in vitro and in vivo. HepG2 cells overexpressing TM4SF1 showed reduced apoptosis and increased cell migration in vitro and enhanced tumor growth and metastasis in vivo, whereas siRNA-mediated silencing of TM4SF1 had the opposite effect. TM4SF1 exerts its effect by regulating a few apoptosis- and migration-related genes including caspase-3, caspase-9, MMP-2, MMP-9 and VEGF. These results indicate that TM4SF1 is associated with liver tumor growth and progression, suggesting that TM4SF1 may be a potential target for treatment of liver cancer in future.     

Semisynthetic Ursolic Acid Fluorolactone Derivatives Inhibit Growth with Induction of p21(waf1) and Induce Apoptosis with Upregulation of NOXA and Downregulation of c-FLIP in Cancer Cells

A series of ursolic acid ((1S,2R,4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)‐10‐hydroxy‐1,2,6a,6b,9,9,12a‐heptamethyl‐2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b‐tetradecahydro‐1H‐picene‐4a‐carboxylic acid) derivatives with a 12‐fluoro‐13,28β‐lactone moiety were synthesized using the electrophilic fluorination reagent Selectfluor. The antiproliferative effects of these novel compounds were evaluated in AsPC‐1 pancreatic cancer cells, and the structure–activity relationships (SARs) were evaluated. Of the compounds synthesized, ursolic acid derivatives carrying a heterocyclic ring, such as imidazole or methylimidazole, and cyanoenones were among the more potent inhibitors of AsPC‐1 pancreatic cancer cell growth. 2‐Cyano‐3‐oxo‐12α‐fluoro‐urs‐1‐en‐13,28β‐olide, compound 20 , was the most effective inhibitor with IC₅₀ values of 0.7, 0.9 and 1.8 μM in pancreatic cancer cell lines AsPC‐1, MIA PaCa‐2 and PANC‐1, respectively. This compound also exhibited better antiproliferative activities against breast (MCF7), prostate (PC‐3), hepatocellular (Hep G2) and lung (A549) cancer cell lines, with IC₅₀ values lower than 1 μM . The mechanism of action by which these compounds exert their biological effect was evaluated in AsPC‐1 cells using the most potent inhibitor synthesized, compound 20 . At 1 μM , the cell cycle arrested at the G1 phase with upregulation of p21^waf1. Apoptosis was induced at an inhibitor concentration of 8 μM with upregulation of NOXA and downregulation of c‐FLIP. These data indicate that fluorolactone derivatives of ursolic acid have improved antiproliferative activity, acting through arrest of the cell cycle and induction of apoptosis.     

One-Pot Three-Component Synthesis of Novel Diethyl((2-oxo-1,2-dihydroquinolin-3-yl)(arylamino)methyl)phosphonate as Potential Anticancer Agents

With the aim of discovering new anticancer agents, we have designed and synthesized novel α-aminophosphonate derivatives containing a 2-oxoquinoline structure using a convenient one-pot three-component method. The newly synthesized compounds were evaluated for antitumor activities against the A549 (human lung adenocarcinoma cell), HeLa (human cervical carcinoma cell), MCF-7 (human breast cancer cell), and U2OS (human osteosarcoma cell) cancer cell lines in vitro, employing a standard 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The results of pharmacological screening indicated that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most compounds showed more potent inhibitory activities comparable to 5-fluorouracil (5-FU) which was used as a positive control. The mechanism of representative compound 4u (diethyl((2-oxo-1,2-dihydroquinolin-3-yl)(phenyl-amino)methyl)phosphonate) indicated that the compound mainly arrested HeLa cells in S and G2 stages and was accompanied by apoptosis in HeLa cells. This action was confirmed by acridine orange/ethidium bromide staining, Hoechst 33342 staining, and flow cytometry.     

Synthesis of functionalized polymeric adsorbent selective to cobalt

Amino derivative of chloromethylated polystyrene resin was synthesized and functionalized by 1,10‐phenanthroline (1,10‐Phen) to yield a novel adsorbent, namely 4‐methylamino‐[N,N‐bis(2,2^′)‐1,10‐phenanthroline] polystyrene ( 4‐MABPPS ). The complete development of novel adsorbent along with its characterization is described in detail. The adsorption ability and selectivity of 4‐MABPPS were investigated for cobalt and zirconium ions so as to efficiently separate cobalt ion impurities from zircalloy cladding material of nuclear reactors. The experimental results showed selective uptake of cobalt by the adsorbent in the presence of zirconium. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Discovery of 6-Arylurea-2-arylbenzoxazole and 6-Arylurea-2-arylbenzimidazole Derivatives as Angiogenesis Inhibitors: Design,Synthesis and in vitro Biological Evaluation

We embarked on a structural optimization campaign aimed at the discovery of novel anti-angiogenesis agents with previously reported imidazole kinase inhibitors as a lead compound. A library of 29 compounds was synthesized. Several title compounds exhibited selective inhibitory activities against vascular endothelial growth factor receptor 2 (VEGFR-2) over epidermal growth factor receptor (EGFR) kinase; these compounds also displayed selective and potent antiproliferative activity against three cancer cell lines. The newly synthesized compounds were evaluated for anti-angiogenesis activity by chick chorioallantoic membrane (CAM) assay. Among them, 1-(2-(2-chlorophenyl)benzo[d]oxazol-5-yl)-3-(4-(trifluoromethoxy)phenyl)urea (compound 5 n ) showed the most potent anti-angiogenesis capacity, efficient cytotoxic activities (in vitro against human umbilical vein endothelial cells (HUVEC), H1975, A549, and HeLa cell lines, with respective IC₅₀ values of 8.46, 1.40, 7.61, and 0.28 μm ), and an acceptable level of VEGFR-2 kinase inhibition (IC₅₀=0.25 μm ). Molecular docking analysis revealed 5 n to be a type II inhibitor of VEGFR-2 kinase. In general, these results indicate that these 6-arylurea-2-arylbenzoxazole/benzimidazole derivatives are promising inhibitors of VEGFR-2 kinase for potential development into anti-angiogenesis drugs.     

DNA binding,cytotoxicity and DNA cleavage promoted by gold(III) complexes

Square planar Au(III) complexes of 2,2′-dipyridylamine (A¹), di(2-pyridyl)ketone (A²), 2-(4-chlorophenyl)-1H-imidazo[4,5-f] [1,10] phenanthroline (A³) and 2-(4-bromophenyl)-1H-imidazo[4,5-f][1,10] phenanthroline (A⁴) of type [Au(Aⁿ)Cl₂].Cl were synthesized and characterized using conductivity measurement, C,H,N elemental analysis, FT-IR, LC–MS, ¹H and ¹³C NMR spectroscopy. The compounds manifested significant cytotoxic properties in vitro for brine shrimp lethality bioassay. The metal complexes were screened for series of DNA binding activity using UV–vis. absorption titration, hydrodynamic measurement and thermal DNA denaturation study. The nucleolytic activity was performed on plasmid pUC19 DNA. The Michaelis–Menten kinetic studies were performed to evaluate rate of enhancement in metal complexes mediated DNA cleavage over the noncatalyzed DNA cleavage.     

A cyclometalated iridium(III) complex that inhibits the migration and invasion of MDA-MB-231 cells

A cyclometalated iridium(III) complex, [Ir(ppy)₂(PCN)]Cl (Ir1, ppy = 2-phenylpyridine, PCN = 2-(4-cyanophenyl)imidazo[4,5-f] [1,10] phenanthroline), was synthesized and characterized in the present study. Ir1 inhibited the proliferation, migration and invasion of MDA-MB-231 human breast cancer cells in a dose-dependent manner. Moreover, Ir1 down-regulated the phosphorylation of AKT/ERK signal pathways. According to confocal fluorescence microscopy analysis, Ir1 was primarily localized within the mitochondria and induced apoptosis through an intrinsic mitochondria-mediated apoptotic pathway. Thus, Ir1 exhibited both antimetastatic and antineoplastic properties, indicating that Ir1 may be a viable drug candidate in antimetastasis and anticancer therapies.     

Investigation of antitumor mechanism of the chiral ruthenium complex Λ-[Ru(phen)2p-MOPIP]2 + in human gastric cancer MGC-803 cells

There has been a vast increase in telomerase inhibition research over the past several years, which was demonstrated as an attractive anti-tumor strategy. Our previous study found that the chiral ruthenium complex, [Ru(phen)₂p-MOPIP]^2 + (Phen = 1,10-phenanthroline, p-MOPIP = 2-(4-methoxyphenyl)-imidazo[4,5f] Markman (2003), Janaratne et al. (2007) phenanthroline) (dl-OMe) and its enantiomer Δ/Λ-[Ru(phen)₂p-MOPIP]^2 + (Δ/Λ-OMe) could bind to and stabilize G-quadruplex DNA structure in telomeres, and inhibit telomerase activity. In this study, cytotoxic activity of these Ru complexes was studied by MTT assay. The anti-tumor mechanisms of Λ-OMe were investigated using TRAP assay, Western blot analysis, flow cytometry, Hochest staining, and RT-PCR. Results showed that among several Ru complexes, Λ-OMe demonstrated a better anti-tumor activity against gastric cancer cell line (MGC-803), and had less effect on normal gastric epithelial cell. Λ-OMe effectively inhibited the cell growth by inhibiting cellular telomerase activity, triggering cell cycle arrest, and inducing apoptosis of MGC-803 cells. The inhibitory effect on telomerase activity was associated with the altered expression of telomere-related proteins TRF1 and TRF2. Cell-cycle arrest was associated with increased levels of P21 mRNA. Apoptosis of MGC-803 cell was triggered by modulating the expression of apoptosis-related genes Bax, Bcl-2, and caspase-3. Overall, the results suggest that Λ-OMe may be a new promising agent for human gastric cancer therapy.     

Metformin and Dichloroacetate Suppress Proliferation of Liver Cancer Cells by Inhibiting mTOR Complex 1

The Warburg effect is important for cancer cell proliferation. This phenomenon can be flexible by interaction between glycolysis and mitochondrial oxidation for energy production. We aimed to investigate the anticancer effects of the pyruvate dehydrogenase kinase inhibitor, dichloroacetate (DCA) and the mitochondrial respiratory complex I inhibitor metformin in liver cancer cells. The anticancer effect of DCA and/or metformin on HepG2, PLC/PRF5 human liver cancer cell lines, MH-134 murine hepatoma cell lines, and primary normal hepatocytes using MTT assay. Inhibition of lactate/ATP production and intracellular reactive oxygen species generation by DCA and metformin was investigated. Inhibition of PI3K/Akt/mTOR complex I was evaluated to see whether it occurred through AMPK signaling. Anticancer effects of a combination treatment of DCA and metformin were evaluated in HCC murine model. The results showed that metformin and DCA effectively induced apoptosis in liver cancer cells. A combination treatment of metformin and DCA did not affect viability of primary normal hepatocytes. Metformin upregulated glycolysis in liver cancer cells, thereby increasing sensitivity to the DCA treatment. Metformin and DCA inhibited mTOR complex I signaling through upregulated AMPK-independent REDD1. In addition, metformin and DCA increased reactive oxygen species levels in liver cancer cells, which induced apoptosis. A combination treatment of metformin and DCA significantly suppressed the tumor growth of liver cancer cells using in vivo xenograft model. Taken together, the combined treatment of metformin and DCA suppressed the growth of liver cancer cells. This strategy may be effective for patients with advanced liver cancer.     

Synthesis of Novel 2-Thiouracil-5-Sulfonamide Derivatives as Potent Inducers of Cell Cycle Arrest and CDK2A Inhibition Supported by Molecular Docking

In an effort to discover potent anticancer agents, 2-thiouracil-5-sulfonamides derivatives were designed and synthesized. The cytotoxic activity of all synthesized compounds was investigated against four human cancer cell lines viz A-2780 (ovarian), HT-29 (colon), MCF-7 (breast), and HepG2 (liver). Compounds 6b,d–g, and 7b showed promising anticancer activity and significant inhibition of CDK2A. Moreover, they were all safe when tested on WI38 normal cells with high selectivity index for cancer cells. Flow cytometric analysis for the most active compound 6e displayed induction of cell growth arrest at G1/S phase (A-2780 cells), S phase (HT-29 and MCF-7 cells), and G2/M phase (HepG2 cells) and stimulated the apoptotic death of all cancer cells. Moreover, 6e was able to cause cycle arrest indirectly through enhanced expression of cell cycle inhibitors p21 and p27. Finally, molecular docking of compound 6e endorsed its proper binding to CDK2A, which clarifies its potent anticancer activity.     

Synthetic Peroxides Promote Apoptosis of Cancer Cells by Inhibiting P-Glycoprotein ABCB5

This article discloses a new horizon for the application of peroxides in medical chemistry. Stable cyclic peroxides are demonstrated to have cytotoxic activity against cancer cells; in addition a mechanism of cytotoxic action is proposed. Synthetic bridged 1,2,4,5-tetraoxanes and ozonides were effective against HepG2 cancer cells and some ozonides selectively targeted liver cancer cells (the selectivity indexes for compounds 11 b and 12 a are 8 and 5, respectively). In some cases, tetraoxanes and ozonides were more selective than paclitaxel, artemisinin, and artesunic acid. Annexin V flow-cytometry analysis revealed that the active ozonides 22 a and 23 a induced cell death of HepG2 by apoptosis. Further study showed that compounds 22 a and 23 a exhibited a strong inhibitory effect on P-glycoprotein (P-gp/ABCB5)-overexpressing HepG2 cancer cells. ABCB5 is a key player in the multidrug-resistant phenotype of liver cancer. Peroxides failed to demonstrate a direct correlation between oxidative potential and their biological activity. To our knowledge this is the first time that peroxide diastereoisomers have been found to show stereospecific antimalarial action against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Stereoisomeric ozonide 12 b is 11 times more active than stereoisomeric ozonide 12 a (IC₅₀=5.81 vs 65.18 μm ). Current findings mean that ozonides merit further investigation as potential therapeutic agents for drug-resistant hepatocellular carcinoma.     

Synthesis of phenanthroline derivative by Suzuki coupling reaction and the use of its ruthenium complex as an optical pH sensor

A phenanthroline derivative, which has an aniline group, was synthesized by palladium catalyzed Suzuki cross coupling reactions. The aryl phosphine ligand, PPh_3, showed higher activity than the alkyl phosphines, P(^tBu)₃ and PCy_3, in the Suzuki couplings and provided the coupled product, 4-phenyl-7-(4′-amino-biphenyl-4-yl)-[1,10]phenanthroline (5), with 73% yield. Its ruthenium complex, bis(4,7-diphenyl-[1,10]phenanthroline){4-phenyl-7-(4′-amino-biphenyl-4-yl)-[1,10]phenanthroline} ruthenium(II) bis(hexafluorophosphate) (8), was synthesized under mild conditions. This complex showed a linear fluorescence intensity response between pH 3.5 and pH 8.5.     

Synthesis and Pharmacological In Vitro Investigations of Novel Shikonin Derivatives with a Special Focus on Cyclopropane Bearing Derivatives

Melanoma is the deadliest form of skin cancer and accounts for about three quarters of all skin cancer deaths. Especially at an advanced stage, its treatment is challenging, and survival rates are very low. In previous studies, we showed that the constituents of the roots of Onosma paniculata as well as a synthetic derivative of the most active constituent showed promising results in metastatic melanoma cell lines. In the current study, we address the question whether we can generate further derivatives with optimized activity by synthesis. Therefore, we prepared 31, mainly novel shikonin derivatives and screened them in different melanoma cell lines (WM9, WM164, and MUG-Mel2 cells) using the XTT viability assay. We identified (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl 2-cyclopropyl-2-oxoacetate as a novel derivative with even higher activity. Furthermore, pharmacological investigations including the ApoToxGlo^TM Triplex assay, LDH assay, and cell cycle measurements revealed that this compound induced apoptosis and reduced cells in the G1 phase accompanied by an increase of cells in the G2/M phase. Moreover, it showed hardly any effects on the cell membrane integrity. However, it also exhibited cytotoxicity against non-tumorigenic cells. Nevertheless, in summary, we could show that shikonin derivatives might be promising drug leads in the treatment of melanoma.     

New photocatalyst for the degradation of organic dyes based on [Co2(1,4-BDC)(NCP)2]n·4nH2O

One metal–organic framework, [Co₂(1,4-BDC)(NCP)₂]_n·4nH₂O (1) (1,4-H₂BDC denotes benzene-1,4-dicarboxylic acid, HNCP denotes 2-(4-carboxyphenyl)imidazo(4,5-f)(1,10)phenanthroline), has been hydrothermally synthesized and characterized via single crystal X-ray diffraction, powder X-ray diffraction, thermogravimetric analysis and diffuse-reflectance UV–vis spectrum study. Compound 1 shows a 2D layer structure, which is further extended into a 3D supramolecular network structure through π–π stacking interactions. The photocatalytic study on compound 1 indicates that it is an active catalyst for the degradation of orange G, rhodamine B, methylene blue and methyl violet.     

Design,Synthesis and Evaluation of Novel Derivatives of Curcuminoids with Cytotoxicity

Curcumin and curcuminoids have been discussed frequently due to their promising functional groups (such as scaffolds of α,β-unsaturated β-diketone, α,β-unsaturated ketone and β′-hydroxy-α,β-unsaturated ketone connected with aromatic rings on both sides) that play an important role in various bioactivities, including antioxidant, anti-inflammatory, anti-proliferation and anticancer activity. A series of novel curcuminoid derivatives (a total of 55 new compounds) and three reference compounds were synthesized with good yields using three-step organic synthesis. The anti-proliferative activities of curcumin derivatives were examined for six human cancer cell lines: HeLaS3, KBvin, MCF-7, HepG2, NCI-H460 and NCI-H460/MX20. Compared to the IC₅₀ values of all the synthesized derivatives, most α,β-unsaturated ketones displayed potent anti-proliferative effects against all six human cancer cell lines, whereas β′-hydroxy-α,β-unsaturated ketones and α,β-unsaturated β-diketones presented moderate anti-proliferative effects. Two potent curcuminoid derivatives were found among all the novel derivatives and reference compounds: (E)-5-hydroxy-7-phenyl-1-(3,4,5-trimethoxyphenyl)hept-1-en-3-one (compound 3) and (1E,4E)-1,7-bis(3,4,5-trimethoxyphenyl)hepta-1,4-dien-3-one (compound MD12a). These were selected for further analysis after the evaluation of their anti-proliferative effects against all human cancer cell lines. The results of apoptosis assays revealed that the number of dead cells was increased in early apoptosis and late apoptosis, while cell proliferation was also decreased after applying various concentrations of (E)-5-hydroxy-7-phenyl-1-(3,4,5-trimethoxyphenyl)hept-1-en-3-one (compound 3) and (1E,4E)-1,7-bis(3,4,5-trimethoxyphenyl)hepta-1,4-dien-3-one (compound MD12a) to MCF-7 and HpeG2 cancer cells. Analysis of the gene expression arrays showed that three genes (GADD45B, SESN2 and BBC3) were correlated with the p53 pathway. From the quantitative PCR analysis, it was seen that (1E,4E)-1,7-bis(3,4,5-trimethoxyphenyl)hepta-1,4-dien-3-one (compound MD12a) effectively induced the up-regulated expression of GADD45B, leading to the suppression of MCF-7 cancer cell formation and cell death. Molecular docking analysis was used to predict and sketch the interactions of the GADD45B-α,β-unsaturated ketone complex for help in drug design.     

铁棒锤总生物碱、3-乙酰乌头碱和宋果灵抗肿瘤活性研究

本文从铁棒锤总生物碱中提取分离得到3-乙酰乌头碱和宋果灵,应用MTT比色法研究药物的细胞毒型、细胞形态学实验方法观察细胞形态、流式细胞术分析细胞凋亡和细胞周期,激光共聚焦从形态上分析细胞的凋亡等多方面对其抑制人肝癌细胞的生理活性进行研究。3-乙酰乌头碱和宋果灵的抗肿瘤细胞研究表明,随着浓度的逐步增加,其抗肿瘤效果逐步增强;药物作用于人肝癌细胞后,细胞数量明显减少,具有明显的抑制HepG2生长的能力,并且使细胞发生早期凋亡和晚期凋亡的比率增大,随处理时间的延长细胞G1期细胞逐渐增多,G2期和S期细胞逐渐减少。3-乙酰乌头碱和宋果灵的体外抗肿瘤实验研究初步证实了其具有抑制肿瘤细胞增殖、诱导肝癌细胞凋亡的作用,显示3-乙酰乌头碱和宋果灵可能成为新的肝癌细胞凋亡诱导剂,为寻找新型抗肿瘤药物的先导化合物奠定了基础。     

L-蛋氨酸多吡啶铜(Ⅱ)三元配合物的合成及与DNA的相互作用

文章合成了三种L-蛋氨酸多吡啶铜(II)三元混配配合物,[Cu(Met)(Phen)(ClO4)](ClO4)(1)(Phen=1,10-菲咯啉),[Cu(Met)(IP)(ClO4)](ClO4)(2)(IP=咪唑并[4,5-f]1,10-菲咯啉)和[Cu(Met)(PIP)(ClO4)](ClO4)(3)(PIP=2-苯基-咪唑并[4,5-f]1,10-菲咯啉)。采用电子吸收光谱和荧光光谱等方法研究了配合物与小牛胸腺DNA的相互作用,用凝胶电泳方法研究了配合物对pBR322DNA的氧化切割活性。结果表明,虽配合物与DNA的作用较弱,但多吡啶配体的平面大小可直接影响到配合物与DNA的相互作用,而氨基酸辅助配体可起到进一步的调控作用。