New application of human tumor clonogenic assay to in vitro evaluation of tumor-targeting efficiency of immunoconjugates.

This report proposes an efficient in vitro method for the evaluation of drug targeting with monoclonal antibody as a carrier to tumor cells. Monoclonal antibody (35G; IgG2a) selectively binding to alpha-fetoprotein (AFP) from human hepatoma cells (HuH-7) was conjugated with an anticancer drug, vindesine (VDS). Human tumor clonogenic assay (HTCA) with some modifications was applied to estimate the targeting efficiency of a conjugate (VDS-35G) for the first time. In this assay, VDS-35G was cytotoxically active against HuH-7 cells at a lower concentration (0.5 ng/ml) and for a shorter contact time than VDS (50 ng/ml), while 35G and VDS-normal mouse immunoglobulin conjugate (VDS-n-IgG) were not active against the cells. Both VDS-35G and VDS-n-IgG were inactive against HuH-13 cells established from a human hepatocellular carcinoma producing no AFP. In the conventional monolayer culture assay (MCA), VDS-35G showed little effect on HuH-7 cells at the concentration effective in HTCA. The cytotoxic activity of VDS in MCA was similar to that in HTCA but the cytotoxic activity of VDS-35G in MCA was considerably different from that in HTCA. This discrepancy could be explained by the hypothesis that VDS-35G was directed at stem cells of the HuH-7 cell population sensitively and selectively. HTCA was shown to be a useful in vitro evaluation method for drug targeting.     

Photocatalytic activity of water-soluble tetrapyrrole compounds in the presence of amino-containing polymers

It was demonstrated that the activity of tetrapyrrole photosensitizers (TPSs) of singlet oxygen generation (dimegin, tetrasulfophenylporphyrin, and photoditasine) in the oxidation of tryptophan in the aqueous phase decreases in the presence of polymers containing free amino groups (chitosan and polyallylamine). The decrease of the activity is accompanied by the change of the electronic absorption spectra of the TPSs. Analogues of chitosan with screened amino groups (chitosan sulfate and carboxymethylchitin) or without amino groups (carboxymethylcellulose), as well as hexamethylenediamine, a low-molecular-weight compound, do not affect the activity of the TPSs. The regularities observed can be accounted for by the association of molecules of the tetrapyrroles initiated by the complexation of the TPSs having external salt groupings with free amino groups of the polymers.     

Study on the activity and mechanism of skimmianine against human non-small cell lung cancer

The present research was to investigate the effects of skimmianine (SK) in four non-small cell lung cancer (NSCLC) cells. We found that SK can significantly inhibit the growth of NSCLC cells and markedly induce apoptosis in NSCLC cells. The effects of growth inhibition and apoptosis induction were in a concentration–response relationship and caspase-dependent manner.     

Synthesis and anti-brucella activity of some new 1,3,4-oxadiazole derivatives containing a ferrocene unit

An isocyanide-based multicomponent reaction between cinnamic acid derivatives or 3-phenyl-2-propynoic acid, (N-isocyanimino)triphenylphosphorane, ferrocenecarbaldehyde, and dibenzylamine has been reported in excellent yields for the preparation of some new ferrocenyl-containing 1,3,4-oxadiazole derivatives. The anti-brucella activities of the products are investigated in in vitro and in vivo assays.     

Synthesis and antimicrobial activity of some novel ferrocene-based Schiff bases containing a ferrocene unit

In the present investigation, a series of ferrocene-based Schiff bases 5a?Cm were synthesized by the condensation of various chalcones 3a?Cm with S-benzyl dithiocarbazate in absolute ethanol using catalytic amount of glacial acetic acid, and characterized by element analysis,¹H NMR,¹³C NMR, and IR. The synthesized compounds were screened for their in vitro antimicrobial activity against four bacterias (Staphylococcus aureus ATCC 9144, Bacillus cereus ATCC 11778, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 43288) and two fungals (Aspergillus niger ATCC 9092 and Aspergillus fumigatus ATCC 46645) strains. The Schiff bases 5g, 5h, and 5m against Gram-positive bacterial (E. coli and P. aeruginosa) strains was found to be higher than that for the standard drug. They are potential new drugs in antibacterial activity aspects in further days.     

Study of the biological activity of novel synthetic compounds with antiviral properties against human rhinoviruses

Picornaviridae represent a very large family of small RNA viruses, some of which are the cause of important human and animal diseases. Since no specific therapy against any of these viruses currently exists, palliative symptomatic treatments are employed. The early steps of the picornavirus replicative cycle seem to be privileged targets for some antiviral compounds like disoxaril and pirodavir. Pirodavir's main weakness is its cytotoxicity on cell cultures at relatively low doses. In this work some original synthetic compounds were tested, in order to find less toxic compounds with an improved protection index (PI) on infected cells. Using an amino group to substitute the oxygen atom in the central chain, such as that in the control molecule pirodavir, resulted in decreased activity against Rhinoviruses and Polioviruses. The presence of an -ethoxy-propoxy- group in the central chain (as in compound I-6602) resulted in decreased cell toxicity and in improved anti-Rhinovirus activity. This compound actually showed a PI >700 on HRV14, while pirodavir had a PI of 250. These results demonstrate that modification of pirodavir's central hydrocarbon chain can lead to the production of novel derivatives with low cytotoxicity and improved PI against some strains of Rhinoviruses.     

Biological activity of some sulfur- and selenium-containing spiro compounds

Russian Chemical Bulletin - Cytotoxicity to K-562 leukemia cell line of two spiro compounds containing selenium or sulfur atom in their structure were compared....     

Evaluation of structural,spectral characterization and in vitro cytotoxic activity studies of some polycyclic aromatic compounds

The present study aims to introduce three known and three new stable polycyclic aromatic compounds synthesized. With MALDI-Mass, ¹H and ¹³C NMR spectroscopy, all new compounds were characterized. In the DMF solution were carried out the electrochemical and photophysical properties of the polyaromatic compounds. The compounds are highly fluorescent showing green-red emission when excited at one single wavelength. For the compound 3, it was shown that the highest Stokes Shift (191 nm) appeared which may be due to the excited state energy transfer. The compounds also indicated the blue-orange region of the electromagnetic spectrum strong emission bands. Additionally, compounds 1, 3, 4, and 5 were investigated for their in vitro cytotoxic activities against PC-3 prostate cancer cells, L-929 non-cancerous cells, and MDA-MB-231 breast cancer for 24 h, 48 h and 72 h. The results obtained from the experiment demonstrated that compounds had different cytotoxic activity against cell lines. Compound 3 was indicated to be inactive against L-929 cells and MDA-MB-231 cancer cells, whereas compounds 1, 4 and 5 indicated a dose and time-dependent cytotoxic activity against PC-3, MDA-MB-231, and L-929 cell lines. It was found that the most sensitive cells to compound 5 were MDA-MB-231 human breast cancer cells. Additionally, it became clear that compounds 1 and 3 had significant selectivity for human PC-3 prostate cancer cells, and compounds 1, 4 and 5 had considerable selectivity for human MDA-MB-231 breast cancer cells. Also, the quantum chemical examinations of six organic compounds were conducted at the B3LYP/6-31G level in the gas phase and water. According to calculated results, compound 5 was found to be the best candidate for NLO applications.     

Host-guest inclusion for enhancing anticancer activity of pemetrexed against lung carcinoma and decreasing cytotoxicity to normal cells

Advanced chemotherapy strategies are in urgent demand for improving anticancer efficacy. Herein, a water-soluble pillar[6]arene (WP6A) was used to load chemotherapeutic agent pemetrexed (PMX) by forming direct host-guest inclusion, which is beneficial for decreasing cytotoxicity of PMX on BEAS-2B cells. NMR and florescence titration served to confirm the complexation between WP6A and ATP with higher affinity [(5.67 ± 0.31) × 10⁵ L/mol], favoring competitive replacement of PMX. Complexation ATP by WP6A effectively prevented ATP from being hydrolyzed in presence of alkaline phosphatase. The formed host-guest complex was further used to block the efflux pump by cutting off energy source from ATP hydrolysis, which was accompanied with releasing PMX to produce synergistic enhancement of anticancer performance towards A549 cells. This supramolecular strategy would also be extended to other clinical chemotherapeutic agents and it was expected to provide salutary profits for cancer patients.     

Synergistic enhanced photocatalytic and photothermal activity of Au@TiO2 nanopellets against human epithelial carcinoma cells

The photocatalytic and plasmonic photothermal cancer cell-killing activity of the metallic Au-capped TiO(2) (Au@TiO(2)) composite colloidal nanopellets has been investigated on HeLa cells under UV-visible (350-600 nm) light irradiation. The Au@TiO(2) composite nanopellets with the uniform Au-capped TiO(2) structure were successfully synthesized by simple reduction of HAuCl(4) on the surface of TiO(2) nanoparticles. The morphological structure and surface properties of Au@TiO(2) were characterized by using UV-visible absorption spectroscopy, TEM, SEM, XPS, EDX and XRD analyses. The formation of hydroxyl radicals (˙OH) was confirmed by photoluminescence (PL) spectra. The photocatalytic and photothermal cell-killing activity of the Au@TiO(2) nanopellets was found to vary with the molar ratio of Au to TiO(2). The direct involvement of the metal particles in mediating the electron transfer from the photoexcited TiO(2) under the band gap excitation is considered to carry out the efficient photocatalytic reaction on the cells. The plasmonic absorption spectra of Au@TiO(2) suspensions were also measured for the evaluation of photothermal cell killing. The charge separation, the interfacial charge-transfer and photothermal activity promoted the photocatalytic-photothermal cancer-cell killing more than TiO(2) alone. The cytotoxic effect of Au@TiO(2) nanopellets with low concentration of gold (TiO(2) : Au molar ratio > 1 : 1) was found to be 100%, whereas that of the commercial TiO(2) (P25) was ca. 50%. The comparative study of the cell viability using Au alone and TiO(2) alone revealed that the synergistic effect of photocatalytic hydroxyl radical formation and Au-plasmonic photothermal heat generation plays a vital role in the cancer cell killing. A plausible mechanism was also proposed for photocatalytic cancer cell killing based on the obtained results.     

Synthesis and biological activity of the pinostrobin oxime complex compounds with some d-metals

The process of the complex formation by the natural flavonoid pinostrobin (5-hydroxy-7-methoxyflavonone) oxime with the Cu(II) and Fe(III) ions in a water-ethanol medium was investigated. The metal: ligand ratio in the complex was determined by the saturation method. The results of the analysis of IR spectra and the data of mass-spectrometric studies of the structure of the obtained complex compounds are reported. The antiviral activity of the synthesized complexes with respect to the human immunodeficiency virus HIV-1 IIIB and HIV-2 ROD strains was studied. The antioxidant activity of the complexes, as well as the parent pinostrobin oxime ligand, was evaluated with respect to the diphenylpicrylhydrazyl (DPPH) radical and the 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid (ABTS) radical cation.     

Separation of haem compounds by reversed-phase ion-pair high-performance liquid chromatography and its application in the assay of ferrochelatase activity

The separation of haems and porphyrins was achieved in a reversed-phase ion-pair high-performance liquid chromatography system using tetrabutylammonium hydrogen sulphate as the pairing ion. The concentration of methanol and pH in the mobile phase were determinative parameters for the elution pattern of the compounds. Two isocratic systems--one for the assay of protohaem IX and one for deuterohaem IX--were developed. The chromatographic systems were applied to the assay of ferrochelatase activity in mitochondria using either protoporphyrin or deuteroporphyrin as the substrate. The ferrochelatase activity was also measured in reticulocytes, which contain high levels of endogenous haem.     

Oxidation of ferrocene and some substituted ferrocenes in the presence of horseradish peroxidase

The enzyme catalysed oxidation of ferrocene and some substituted ferrocenes to the corresponding ferricinium ions by hydrogen peroxide in the presence of native or immobilized horseradish peroxidase has been studied. Initial and maximum rates of oxidation have been determined. It was found that the oxidation was independent of the hydrogen peroxide concentration. The oxidation of ferrocene was effected also by horseradish peroxidase in a coupled system with glucose oxidase in the absence of any added hydrogen peroxide.     

Synthesis,characterization, and antimicrobial activity of novel heterocyclic compounds containing a ferrocene unit via Michael addition reaction

Research on Chemical Intermediates - A series of novel heterocyclic compounds containing a ferrocene unit were synthesized by reacting ferrocenylchalcone with pyrazolyl amine or triazolyl amine via...     

Antibacterial characteristics and activity of water-soluble chitosan derivatives prepared by the Maillard reaction

The antibacterial activity of water-soluble chitosan derivatives prepared by Maillard reactions against Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, Escherichia coli, Shigella dysenteriae, and Salmonella typhimurium was examined. Relatively high antibacterial activity against various microorganisms was noted for the chitosan-glucosamine derivative as compared to the acid-soluble chitosan. In addition, it was found that the susceptibility of the test organisms to the water-soluble chitosan derivative was higher in deionized water than in saline solution. Metal ions were also found to reduce the antibacterial activity of the water-soluble chitosan derivative on S. aureus. The marked increase in glucose level, protein content and lactate dehydrogenase (LDH) activity was observed in the cell supernatant of S. aureus exposed to the water-soluble chitosan derivative in deionized water. The results suggest that the water-soluble chitosan produced by Maillard reaction may be a promising commercial substitute for acid-soluble chitosan.     

Qualitative screening of phenolic compounds in olive leaf extracts by hyphenated liquid chromatography and preliminary evaluation of cytotoxic activity against human breast cancer cells

In this work, high-performance liquid chromatography (HPLC) coupled to electrospray time-of-flight mass spectrometry (ESI-TOF-MS) and electrospray ion trap multiple-stage tandem mass spectrometry (ESI-IT-MS²) has been applied to screen phenolic compounds in olive leaf extracts. The use of a small particle size C18 column (1.8 μm) provided great resolution and made separation of a lot of isomers possible. The structural characterization was based on accurate mass data obtained by ESI-TOF-MS, and the nature of fragmentation ions were further confirmed by ESI-IT-MS² when possible. In addition, we employed tetrazolium salt (MTT)-based assays to assess the effects of olive leaf extracts on the growth of human tumor-derived cells. Upon this approach, we achieved an accurate profile of olive leaf phenolics along with the identification of several important isomers of secoiridoids and flavonoids. This will allow a better understanding of the complete composition of olive-leaf-bioactive compounds as well as their involvement in Olea europaea L. biochemical pathways. Importantly, olive leaf extracts exhibited dose-dependent inhibitory effects on the metabolic status (cell viability) of three breast cancer models in vitro. Since the tumoricidal activity of the extracts should be mainly attributed to the identified olive leaf phenolics, these findings warrant further investigation at the structure–function molecular level to definitely establish the anticancer value of these phytochemicals.