Functionalised cyclopentadienyl zirconium compounds as potential anticancer drugs

New neutral and ionic functionalised zirconocene dichloride compounds have been isolated and characterised. The ionic zirconocene exhibits excellent cytotoxicity against a range of human tumour cell lines, which represents the first active anticancer zirconocene dichloride compound.     

Functionalised cyclopentadienyl titanium compounds as potential anticancer drugs

A number of new ionic titanocene compounds have been isolated and characterised, which exhibit excellent cytotoxicity against different human tumour cell lines including a defined cisplatin resistant cell line. A range of biological assays have been carried out to determine levels of cytotoxicity and levels of DNA interstrand crosslinking.     

非铂类金属抗癌化合物的研究进展

综述了除铂配合物外其它金属抗癌化合物的发现、临床应用、抗癌机理及研究现状。     

Peptidomimetics and metalloprotease inhibitors as anticancer drugs

Peptidomimetics with three types, as the structural or functional mimetics of natural active peptides, can preserve the bioactivity and improve the bioavailability and the specificity towards the targets of the lead peptides. Peptidomimetics of high bioactivity can be designed through various ways including conformation restriction, modification and non-peptide design. Recently the concentration on the development of cancer chemotherapeutic drugs was transferred from cytotoxic drugs to target-based drugs, and many proteases and peptidases that play key roles in the process of tumor genesis and development was discovered, which means that peptidomimetics as potential cancer chemotherapeutic drugs should be paid close attention to. Our laboratory has focused on the development of small-molecule peptidomimetic inhibitors of APN, MMPs and HDACs as target-based anticancer agents. These three zinc-dependent metalloproteinases play very important roles in the process of tumor genesis, invasion, metastasis, angiogenesis and matrix degradation, so small-molecule peptidomimetic inhibitors based on them would be quite potential in the development of chemotherapeutic drugs with high selectivity. Supported by the National High Technology Research and Development Program of China (863 Project) (Grant No. 2007AA02Z314), the National Natural Science Foundation of China (Grant Nos. 90713041 & 30772654), and the Doctoral Fund of Ministry of Education of China (Grant No. 20060422029)     

牛心朴子草植物农药的化学成分与生物活性研究

在分离鉴定化学组分基础上结合普筛农药活性,发现牛心朴子草提取物中生物碱部位显示抗植物病毒极高活性。通过生物活性跟踪与色谱分离、结构鉴定,确定它是菲并吲哚里西啶生物碱,包括7-脱甲氧基娃儿藤碱(Antofine)(1)和N-氧代-7-脱甲氧基娃儿藤碱(N-Oxideantofine)(2)。其中2是首次从该草分离得到。Antofine(1)是该草抑制植物病毒主要成份;半中枯斑法测定它在10^-^6g/mL浓度的枯斑抑制率达60%,比对照的常用植物病毒抑制剂活性高1～2个数量级。用多种生测方法验证该草生物碱试样抗植物病毒如烟草花叶病毒(TMV)、马铃薯Y病毒(PVY)、芜菁花叶病毒(TuMV)等的生物活性。     

Ruthenium anticancer compounds: myths and realities of the emerging metal-based drugs

Ruthenium anticancer drugs have attracted an increasing interest in the last 20 years and two of them have entered clinical trials. Compared to platinum drugs, the complexes based on ruthenium are often identified as less toxic and capable of overcoming the resistance induced by platinum drugs in cancer cells. These activities were attributed to the transportation to tumour cells by transferrin and to the selective activation to more reactive species by the reducing environment of solid tumours as compared to healthy tissues. Ruthenium anticancer drugs have been almost always designed to mimic platinum drugs, particularly for targeting DNA. Indeed, none of the above properties has never been clearly demonstrated even for the ruthenium drugs that entered clinical trials. The suggestion for the future is to change the perspective when designing new chemical entities, abandoning the philosophy that guided the actual panel of ruthenium drugs and to look further into the fine mechanism by which the most relevant ruthenium complexes available kill the target tumour cells, then focusing on targets selective of tumour cells and responsible for cell growth and malignancy.     

聚合物胶束型抗癌药物给药系统研究进展

综述了聚合物胶束的性质、制备、以及影响胶束性能的因素,对聚合物胶束在抗肿瘤药物药系统中的研究实例作了简要介绍。     

Review of DBS methods as a quantitative tool for anticancer drugs

An overview of published dried blood spot (DBS) methods for the quantitation of various classes of anticancer drugs from clinical and preclinical studies is presented. The increased reporting of DBS methods in the literature for quantitation of various classes of drugs is a testimony to their utility in bioanalytical applications. While DBS offers several advantages as compared with conventional wet sampling techniques, there remain a number of nuances that may impede the assay adaptability of DBS method in routine quantitative bioanalysis. This review covers several case studies of DBS application in the quantitation of anticancer drugs. Some perspectives are provided on the optimization of the DBS method with respect to the selection of DBS card, spot volume, hematocrit effect and other regular validation parameters, which are essential in quantitative bioanalysis. Some thoughts are provided on the existing gaps in the DBS method and possible remedial measure(s) to address such gaps. Although DBS methods have great potential, there is the need for a global consensus including regulatory support on the type of validation experiments to be performed to support quantitative data.     

Interaction of some steroid drugs with beta-cyclodextrin polymer.

The interaction of 15 steroidal drugs with a water-soluble beta-cyclodextrin polymer was studied by reversed-phase thin-layer chromatography in the absence and in the presence of 0.1 M sodium chloride. The relative strength of interaction was calculated and the relationship between the hydrophobicity parameters of the drugs and the strength of the drug-beta-cyclodextrin polymer was elucidated by principal component analysis. Drugs readily formed inclusion complexes with the cyclodextrin derivatives; the strength of the interaction was higher in the presence of sodium chloride. It was assumed that the formation of inclusion complexes may influence the behaviour of the drugs resulting in modified biological efficacy.     

Novel nanogels as drug delivery systems for poorly soluble anticancer drugs

Two types of novel nanogels were prepared using shell cross-linking of Pluronic F127 micelles with polyethylenimine (PEI) (F127/PEI nanogel), and penetrating network of poly(butylcyanoacrylate) (PBCA) in Pluronic F127 micelles (F127/PBCA nanogel). Poorly soluble anticancer drug, paclitaxel (PTX) and 10-hydroxycamptothecin (HCPT), were used as model drugs and incorporated into nanogels. The results obtained from FT-IR spectroscopy confirmed that the drugs were molecularly dispersed in the nanogels. DLS measurements demonstrated that the nanogel size distribution was narrow with average diameter less than 200 nm. TEM images indicated that the nanogels were spherical in shape and had smooth surfaces. The drug-loaded nanogels showed sustained release profiles compared with the free drugs as revealed by in vitro release experiments. Cytotoxicity tests showed that the cytotoxicity of drug-loaded nanogels against cancer cell in vitro was much higher than that of the free drug. The data demonstrate that these novel nanogels improved stability towards dilution, increased solubility and showed better cellular uptake by cells compared with free drug.     

Synthesis and bioactivity evaluation of new pyrimidinone-5-carbonitriles as potential anticancer and antimicrobial agents

Research on Chemical Intermediates - New series of pyrimidinone-5-carbonitriles 3a–i, 4a–e, 5a–c, 6 and 7 have been synthesized and explored for their activities as anticancer,...     

Synthesis and biological evaluation of glyco-GA compounds as anticancer agents

A series of novel glyco-gambogic acid（GA） compounds were synthesized and evaluated for their in vitro anti-proliferative activity against human hepatocellular carcinoma（HCC） cells.All compounds showed much better aqueous solubility（0.92- 1.89 mg/mL） than GA（0.013 mg/mL）,and displayed potent inhibition on HCC cells(IC₅₀:0.21-12.23μmol/L) and little affects on non-tumor liver cells(IC₅₀:42.56-86.43μmol/L),suggesting that glyco-GA compounds selectively inhibit HCC proliferation,and may be promising candidates for further intensive study.     

Determination of some anticancer 6-thiopurine compounds by high-performance liquid chromatography with micelles as the mobile phase

Aqueous solutions of the anionic surfactant sodium dodecyl sulfate are evaluated as mobile phases for the reversed-phase liquid chromatographic separation of the anti-cancer drugs 6-mercaptopurine and 6-thioguanine, and three of their metabolites (6-mercaptopurine riboside, 6-thioguanine riboside and 6-thioxanthine). The pertinent chromatographic parameters are determined and the effect of organic modifiers or temperature on retention and efficiency is evaluated. The resulting chromatographic procedure allows the determination of two or three of the analytes investigated in serum without any sample preatreatment.     

Functional analysis of repositioned anilide derivatives as anticancer compounds

Off the different types cancers 40% of the population have been observed to be affected by leukemia. Contemporary therapeutics is focusing on generation of new synthetic analogues that can exert maximum positive physiological effect with minimum dosage and negligible deleterious side effects. New generation pharmacists are focusing on such promising effects of Imatinib (a potential anti-cancer drug molecule), Dasatinib, Pelitinib and Nilotinib. The present research study focuses on novel synthesized anilides derivative against BCR-ABL kinase as potential anti-leukemic agent. Validation of the compounds by molecular docking with specific BCR-ABL kinase confirmed their activity. Toxicity prediction of these compounds helped to identify sustainability as therapeutic molecules. The IC₅₀ values were calculated (211 ug, 175 ug, 272ug for compounds A, B, C resp.) and the mode of cell death was gauged by DNA laddering assay. The cells were observed to be induced for programmed cell death. By validating and in-vivo testing of three synthesized compounds, the compound B was observed to be more stable thermodynamically with a potentially vital active site and appears to be a promising anti-leukemic factor. The present research thus lays a preliminary platform in world of pharmaceutics, where these new analogues appear to be efficient, target specific and less toxic molecules.     

Library of second-generation cycloruthenated compounds and evaluation of their biological properties as potential anticancer drugs: passing the nanomolar barrier

A library of 32 organoruthenium compounds has been synthesised. Known and novel C-N cyclometalated compounds as well as N-C-N and N-N-C pincer derivatives of this metal have been used in this purpose. Most of the compounds have been tested for their in vitro antitumoral behaviours, good to excellent activities have thus been found. Several of the newly synthesized compounds pass the symbolic barrier of the nanomolar range for their IC(50) indicating a critical improvement. The level of activity is tentatively correlated to physicochemical properties of the compounds such as their Ru(III/II) redox potential and their lipophilicity (log P).     

Synthesis and anticancer activities of porphyrin induced anticancer drugs

In view of the property of porphyrin's accumulation selectively in tumor,the ftorafur was modified by binding a porphyrin block to improve its tumor targeting and reduce its side effects.These novel porphyrin derivatives and metal compounds were synthesized under mild conditions with satisfactory yield,and the constructions of all these new compounds were characterized by UV,IR,MS, ~1H NMR spectra and elementary analysis.Their anticancer activities were evaluated by MTT assay;the results indicated that the anticancer activities of compounds 4a-c were twice as high as that of ftorafur.     

Effect of absorption of low-molecular-weight compounds by some polymer flocculants

The sorption properties of the intramolecular complex - poly(acrylamide) to poly(vinyl alcohol) grafted copolymer (PVA-PAA_N) in block state were investigated with respect to a number of compounds. The relatively small molecules of phenol, phenylalanine in water solution as well as nitrobenzene in hexane are strongly absorbed by PVA-PAA_N films. The large humine acid molecules (sizes are larger by more than ≈ 10 times) are absorbed by PVA-PAA_N very weakly. It was determined the absorption influence on the character of polymer film solution. In a number of cases the oscillation of the dilution and sorption were observed when determining the critical concentrations of guest molecules in the upper layer of polymer films were achieved. The possible mechanisms of absorption were discussed.     

Self-assembling peptide as a potential carrier of hydrophobic compounds

Microcrystals of a hydrophobic cargo were stabilized by EAK16 II, a self-assembling oligopeptide, and suspended in aqueous solution. Pyrene was used as a model hydrophobic compound. Egg phosphatidylcholine (EPC) vesicles were prepared to mimic a cell membrane. Pyrene was released from its EAK16 II coating into EPC vesicles. The excimer decay profiles were acquired. They showed that pyrene is present in the crystalline form when stabilized by EAK16 II, it is molecularly dispersed in EPC vesicles, and it is completely released from its EAK16 II coating into the membrane bilayers. The release of pyrene from the microcrystals coated with EAK16 II into the EPC membrane was followed by fluorescence as a function of time. The amount of pyrene released into the EPC vesicles at a given time was quantified using a calibration curve. The concentration of pyrene released was determined as a function of time, and the concentration-versus-time profile was fitted with one exponential. The rate of pyrene release was found to depend on the peptide-to-pyrene molecular ratio. Higher peptide-to-pyrene ratios lead to slower transfer of pyrene to the lipophilic environment. Scanning electron micrographs demonstrated that a thicker coating on the pyrene crystals results in a slower release. The data presented in this work demonstrate that the self-assembling EAK16 II can stabilize a hydrophobic cargo in aqueous solution and deliver it into a lipophilic environment, and that the rate of transfer can be adjusted by tuning the peptide-to-pyrene ratio.     

Green synthesis of some tetrahydroquinoline derivatives and evaluation as anticancer agents

This study demonstrates the design and synthesis of heterocyclic compounds with diverse biological effects. Using an ionic liquid catalyst, a sonosynthetic approach for the assembly of bis-arylidene cycloalkanone derivatives (bis-chalcones) has been reported. Three cancer cell lines Hepatocellular carcinoma cells (HepG-2), Breast carcinoma cells (MCF-7), and Lung carcinoma cells (A-549) were utilized to investigate the antiproliferative effects of some selected samples. Many evaluated drugs exhibited good to moderate cytotoxicity against the examined cell lines. Notably, the IC₅₀ values for the S-alkyl derivatives ranged from 2.86 to 13.14 µg/mL.