卟啉类化合物抗肿瘤活性研究

卟啉类化合物的光敏疗法具有安全、简便、选择性好、高效、低毒、副作用小等优点。主要的卟啉类光敏剂有血卟啉衍生物、脱镁叶绿酸α及其衍生物、酞菁类化合物。     

四苯甲氧基酞菁锌配合物的合成与表征

目的 合成四苯甲氧基酞菁锌酞菁锌配合物。方法 模板反应法合成。产物采用红外和紫外可见光谱表征。结果 合成了分子碎片3-苯甲氧基邻苯二甲腈和四苯甲氧基酞菁锌配合物。结论 四苯甲氧基酞菁配合物是一种很有潜力光动力治疗光敏剂。     

抗癌金属配合物的研究综述

自从偶然发现顺铂具有抗癌活性以来,金属配合物的药用性引起了人们的广泛关注,开辟了金属配合物抗癌药物研究的新领域。本文综述了不同金属配合物在抗癌药物中的研究应用新进展。     

抗癌金属配合物的研究综述

自从偶然发现顺铂具有抗癌活性以来,金属配合物的药用性引起了人们的广泛关注,开辟了金属配合物抗癌药物研究的新领域.本文综述了不同金属配合物在抗癌药物中的研究应用新进展.     

酞菁光敏剂抗菌效果的实验研究

目的 针对自主研发的酞菁光敏剂材料,开展相关抗菌效果的实验研究.方法 通过化学共价偶联的方式,将酞菁光敏剂附载于纤维素织物,并对其进行光学及机械性能表征;利用稀释平板菌落计数法,观察添加该光敏剂材料的培养物中的活菌数变化,测定其抗菌活性.结果 通过紫外吸收光谱、荧光光谱等性能测定,发现酞菁光敏剂在纤维素表面以单体形式存在;在一定光照条件(150 mW/cm2光源照射10 min)下该光敏剂能快速、有效地杀灭金黄葡萄球菌、大肠杆菌.该光敏剂材料的抗菌率高达99.9％,与对照组相比,差异有统计学意义(P＜0.01).附载于纤维素织物的酞菁光敏剂在水中无明显溶出,说明其具有良好的耐水洗性能.结论 上述自主研发的酞菁光敏剂材料具有较好的抗菌性能,为将来作为抗菌面料进入临床抗菌防护应用奠定基础.     

大黄酸金属配合物的结构及对人肝癌HepG2细胞增殖的抑制作用

目的:以大黄酸和相应金属盐为原料,合成3种金属配合物,并对其结构进行表征,比较其抗癌活性大小。方法:采用核磁共振氢谱法、红外光谱法、紫外光谱法、滴定法、原子吸收光谱法进行结构表征;采用MTT法测试三种配合物对于人肝癌Hep G2细胞的抑制作用。结果:通过光谱法证实有配合物生成,并推测出其可能结构。MTT测试显示配合物和配体均具有一定的抗癌活性,其中大黄酸-Fe(Ⅲ)抗癌活性最强,其IC50值达17.44μg.m L-1,优于配体大黄酸(IC50=116.741μg.m L-1),大黄酸-Cu(Ⅱ)(IC50=54.427μg.m L-1),大黄酸-Cr(Ⅲ)(IC50=63.584μg.m L-1)。结论:大黄酸金属配合物抗癌活性相比配体增强。     

三联吡啶铂（II）配合物的合成及其自组装性质研究

铂金属配合物因其卓著的疗效已迅速发展为临床治疗癌症的重要药物,本文设计并合成了三联吡啶铂（II）配合物1,通过核磁及质谱等实验表征了目标分子的结构,通过温度依赖性核磁、溶剂依赖性紫外可见光谱等实验证明了酰胺分子间的氢键、π-π堆积以及Pt-Pt金属-金属相互作用是配合物1在自组装过程中的主要驱动力,通过透射电镜观测到组装体的形貌为单分子纳米纤维结构,该研究有利于阐明铂类化合物的自组装行为与其抗癌活性的联系性。     

[Ru(phen)2(3,8-2R-phen)]2+(R=OH,H,F)电子结构与抗癌活性研究

用密度泛函(DFT)法,对配合物[Ru(phen)2(3,8-2R-phen)]2+(R=OH,H,F)进行了理论计算研究.探讨了配合物的电子结构与其抗癌活性的关系:主配体上3,8位上F原子的取代有利于配合物与DNA的作用,增加配合物的抗癌活性.计算结果能较好地预测配合物与DNA的作用强度、抗癌活性及指导具有较高抗癌活性配合物的合成.     

FRu（phen）2（3，8—2R—phen）-]^2＋（R=OH，H，F）电子结构与抗癌活性研究

用密度泛函(DFT)法，对配合物[Ru(phen)2(3，8-2R—phen)^2 (R=OH，H，F)进行了理论计算研究。探讨了配合物的电子结构与其抗癌活性的关系：主配体上3，8位上F原子的取代有利于配合物与DNA的作用，增加配合物的抗癌活性。计算结果能较好地预测配合物与DNA的作用强度、抗癌活性及指导具有较高抗癌活性配合物的合成。     

铜(Ⅱ)配合物抗癌活性研究进展

金属配合物抗癌药物的研究已经成为抗肿瘤药物研究的热点之一。越来越多的研究表明铜(Ⅱ)配合物具有较好的抗癌活性。本文在参阅大量文献的基础上,对铜(Ⅱ)配合物的结构特征﹑和铂(Ⅱ)配合物的活性对比、与DNA的作用﹑与氨基酸的共价作用及对癌细胞的诱导凋亡作用等方面作了介绍。     

Physicochemical Properties and Photodynamic Activity of Novel Derivatives of Triarylmethane and Thiazine

Triarylmethane and thiazine dyes have attracted attention as anticancer and antimicrobial agents, due to their structural features and selective localizations. Although these dyes have been initially explored in the context of photodynamic therapy, some of these such as New Fuchsin and Azure B have still not been extensively investigated. For this reason, we evaluated the chemical stability, aggregation effect, and lipophilicity, as well as the photodynamic activity against LM‐2 murine mammary carcinoma cells of five new brominated dyes of triarylmethane and thiazine. These cationic compounds were obtained at high purities and unequivocally characterized by conventional techniques. The introduction of bromine atoms into the chromophoric system of New Fuchsin and Azure B dyes gave rise to a moderate bathochromic shift and increased the lipophilicity, thereby improving their photophysical and photochemical properties for biomedical applications. Moreover, the in vitro photodynamic activity demonstrated that, as the degree of bromination increased, the phototoxicity remained unchanged or decreased. The lower efficiency to inactivate cultured tumor cells may be attributed to the formation of the colorless carbinol pseudobase and aggregation effects for triarylmethane and thiazine dyes, respectively. A promising strategy to reverse the biological activity decrease observed might be the design of third‐generation photosensitizers.     

Peripheral and axial substitution of phthalocyanines with solketal groups: synthesis and in vitro evaluation for photodynamic therapy

Phthalocyanines (Pcs) are a class of photosensitizers (PSs) with a strong tendency to aggregate in aqueous environment, which has a negative influence on their photosensitizing ability in photodynamic therapy. Pcs with either peripheral or axial solketal substituents, that is, ZnPc(sol)8 and Si(sol)2Pc, respectively, were synthesized and their tendency to aggregate as well as their photodynamic properties in 14C and B16F10 cell lines were evaluated. The results were compared to more hydrophilic silicon Pcs, that is, Si(PEG750)2Pc and Pc4. The order of cellular uptake was Pc4 > ZnPc(sol)8 > Si(PEG750)2Pc > Si(sol2)Pc. In contrast, Si(sol2)Pc showed the highest photocytotoxicity, while ZnPc(sol)8 did not show any photocytotoxicity up to a concentration of 10 microM in both cell types. UV/vis spectroscopy showed that Si(sol)2Pc is less prone to aggregation than ZnPc(sol)8, which can explain the lack of photoactivity of the latter. Si(sol)2Pc was predominantly located in lipid droplets, whereas Si(PEG750)2Pc was homogeneously distributed in the cytosol, which is probably the main cause of their difference in photoactivity. The very high photodynamic efficacy of Si(sol)2Pc makes this PS an interesting candidate for future studies.     

Phthalocyanines covalently bound to biomolecules for a targeted photodynamic therapy

Photodynamic therapy (PDT) is a relatively new cytotoxic treatment, predominantly used in anticancer approaches, that depends on the retention of photosensitizers in tumor and their activation after light exposure. This technology is based on the light excitation of a photosensitizer which induces very localized oxidative damages within the cells by formation of highly reactive oxygen species, the most important being singlet oxygen. Many photo-activable molecules have been synthesized such as porphyrins, chlorins and more recently phthalocyanines which present a strong light absorption at wavelengths around 670 nm and are therefore well-adapted to the optical window required for PDT application. However, the lack of selective accumulation of these photo-activable molecules within tumor tissue is a major problem in PDT, and one research area of importance is developing targeted photosensitizers. Indeed, targeted photodynamic therapy offers the advantage to enhance photodynamic efficiency by directly targeting diseased cells or tissues. Many attempts have been made to either increase the uptake of the dye by the target cells and tissues or to improve subcellular localization so as to deliver the dye to photosensitive sites within the cells. The aim of this review is to present the actual state of the development of phthalocyanines covalently conjugated with biomolecules that possess a marked selectivity towards cancer cells; for some of them their photophysical properties and photodynamic activity will be presented.     

Lanthanides as anticancer agents

The application of inorganic chemistry to medicine is a rapidly developing field, and novel therapeutic and diagnostic metals and metal complexes are now having an impact on medical practice. Advances in biocoordination chemistry are crucial for improving the design of compounds to reduce toxic side effects and understand their mechanisms of action. A lot of metal-based drugs are widely used in the treatment of cancer. The clinical success of cisplatin and other platinum complexes is limited by significant side effects acquired or intrinsic resistance. Therefore, much attention has focused on designing new coordination compounds with improved pharmacological properties and a broader range of antitumor activity. Strategies for developing new anticancer agents include the incorporation of carrier groups that can target tumor cells with high specificity. Also of interest is to develop complexes that bind to DNA in a fundamentally different manner than cisplatin, in an attempt to overcome the resistance pathways that have evolved to eliminate the drug. This review focuses on recent advances in developing lanthanide anticancer agents with an emphasis on lanthanide coordination complexes. These complexes may provide a broader spectrum of antitumor activity. They were compared with classical platinum anticancer drugs. Lanthanides are also of interest because of their therapeutic radioisotopes. The dominant pharmacological applications of lanthanides are as agents in radioimmunotherapy and photodynamic therapy.     

Photodynamic therapy agent with a built-in apoptosis sensor for evaluating its own therapeutic outcome in situ

Identifying the extent of apoptosis in cells or tissues after cancer therapy in real time would be a powerful firsthand tool for assessing therapeutic outcome. We combined therapeutic and imaging functions in one agent, choosing photodynamic therapy (PDT) as an appropriate cancer treatment modality. This agent induces photodamage in irradiated cells and simultaneously identifies apoptotic cells by near-infrared fluorescence. This photodynamic therapy agent with a built-in apoptosis sensor (PDT-BIAS) contains a fluorescent photosensitizer used as an anticancer drug, connected to a fluorescence quencher by a caspase-3 cleavable peptide linker. We demonstrated that cleavage of the peptide linker by caspase-3, one of the executioner caspases involved in apoptosis, results in a detectable increase of fluorescence in solution and in cancer cells after PDT treatment. The apoptosis involvement and drug effectiveness were confirmed by Apoptag and cell viability (MTT) assays supporting the ability of PDT-BIAS to induce and image apoptosis in situ.     

In vitro cytotoxicity study of oxaziridines generated after chlordiazepoxide,demoxepam, and desmethylchlordiazepoxide UV irradiation

The cytotoxicity of oxaziridines photogenerated after irradiation of chlordiazepoxide (CDZ) and its metabolites was investigated in vitro by a MTT assay on P388 leukemia and B16 melanoma cell lines and compared with that of the anticancer drug, melphalan. For the longer time-exposure experiment, oxaziridines had the same cytotoxicity as melphalan and this toxicity was higher when oxaziridines were photogenerated in the presence of cells. In conclusion, oxaziridines generated after CDZ, demoxepam, and desmethylchlordiazepoxide ultraviolet irradiation exhibited cytotoxicity activity against cancer cell lines. A possibility of CDZ use within the context of photodynamic therapy as a treatment for small, superficial tumors should not be excluded, because oxaziridines can be generated locally by skin-tumor local irradiation after CDZ topical administration.     

Recent trends in targeted therapy of cancer using graphene oxide-modified multifunctional nanomedicines

Rapid progresses in nanotechnology fields have led us to use a number of advanced nanomaterials (NMs) for engineering smart multifunctional nanoparticles (NPs)/nanosystems (NSs) for targeted diagnosis and therapy of various diseases including different types of malignancies. For the effective therapy of any type of solid tumor, the treatment modality should ideally solely target the aberrant cancerous cells/tissue with no/trivial impacts on the healthy cells. One approach to achieve such unprecedented impacts can be fulfilled through the use of seamless multimodal NPs/NSs with photoacoustic properties that can be achieved using advanced NMs such as graphene oxide (GO). It is considered as one of the most promising materials that have been used in the development of various NPs/NSs. GO-based targeted NSs can be engineered as programmable drug delivery systems (DDSs) to perform on-demand chemotherapy combined with photonic energy for photothermal therapy (PTT) or photodynamic therapy (PDT). In the current review, we provide important insights on the GO-based NSs and discuss their potentials for the photodynamic/photothermal ablation of cancer in combination with anticancer agents.     

Algicidal activity of phthalocyanines--screening of 31 compounds

Phthalocyanines and their analogues show great potential as photodynamic agents producing reactive oxygen species (ROS), especially in medicine. However, their biocidal effects may also be employed to inhibit various undesirable organisms. This study explores their potential algicidal effects. The laboratory tests concern the effects of various phthalocyanine derivatives on the green alga Pseudokirchneriella subcapitata and cyanobacterium Synechococcus nidulans. Their effects on one example of the sensitive nontarget aquatic organism-crustacean Daphnia magna were also screened. Among 31 tested compounds, the cationic phthalocyanines substituted with heterocycle exhibited the strongest effects on phytoplankton species, some of them even below the level of 1 mg/L, while effects on crustaceans ranged from 3.6 to more than 50 mg/L. These results show that some phthalocyanine derivatives can act as potent algicides.     

Dendrimers and dendritic polymers in drug delivery

The unique properties of dendrimers, such as their high degree of branching, multivalency, globular architecture and well-defined molecular weight, make them promising new scaffolds for drug delivery. In the past decade, research has increased on the design and synthesis of biocompatible dendrimers and their application to many areas of bioscience including drug delivery, immunology and the development of vaccines, antimicrobials and antivirals. Recent progress has been made in the application of biocompatible dendrimers to cancer treatment, including their use as delivery systems for potent anticancer drugs such as cisplatin and doxorubicin, as well as agents for both boron neutron capture therapy and photodynamic therapy.     

Glycophthalocyanines as photosensitizers for triggering mitotic catastrophe and apoptosis in cancer cells

Photodynamic therapy (PDT) is a treatment modality for different forms of cancer based on the combination of light, molecular oxygen, and a photosensitizer (PS) compound. When activated by light, the PS generates reactive oxygen species leading to tumor destruction. Phthalocyanines are compounds that have already shown to be efficient PSs for PDT. Several examples of carbohydrate substituted phthalocyanines have been reported, assuming that the presence of carbohydrate moieties could improve their tumor selectivity. This work describes the photoeffects of symmetric and asymmetric phthalocyanines with D-galactose (so-called GPh1, GPh2, and GPh3) on HeLa carcinoma cells and their involvement in cell death. Photophysical properties and in vitro photodynamic activities for the compounds considered revealed that the asymmetric glycophthalocyanine GPh3 is very efficient and selective, producing higher photocytotoxicity on cancer cells than in nonmalignat HaCaT. The cell toxiticy after PDT treatment was dependent upon light exposure level and GPh3 concentration. GPh3 causes cell cycle arrest at the metaphase stage leading to multiple spindle poles, mitotic catastrophe, followed by apoptosis in cancer cells. These effects were partially negated by the pancaspase inhibitor Z-VAD-FMK. Together, these results indicate that GPh3 is an excellent candidate drug for PDT, able to induce selective tumor cell death.