New Symmetrically Esterified m-Bromobenzyl Non-Aminobisphosphonates Inhibited Breast Cancer Growth and Metastases

1 - ArticleBACKGROUND: Although there was growing evidence in the potential use of Bisphosphonates (BPs) in cancer therapy, their strong osseous affinities that contrast their poor soft tissue uptake limited their use. Here, we developed a new strategy to overcome BPs hydrophilicity by masking the phosphonic acid through organic protecting groups and introducing hydrophobic functions in the side chain. METHODOLOGY/PRINCIPAL FINDINGS: We synthesized non-nitrogen BPs (non N-BPs) containing bromobenzyl group (BP7033Br) in their side chain that were symmetrically esterified with hydrophobic 4-methoxphenyl (BP7033BrALK) and assessed their effects on breast cancer estrogen-responsive cells (T47D, MCF-7) as well as on non responsive ones (SKBR3, MDA-MB-231 and its highly metastatic derived D3H2LN subclone). BP7033Br ALK was more efficient in inhibiting tumor cell proliferation, migration and survival when compared to BP7033Br. Although both compounds inhibited tumor growth without side effects, only BP7033Br ALK abrogated tumor angiogenesis and D3H2LN cells-induced metastases formation. CONCLUSION/SIGNIFICANCE: Taken together these data suggest the potential therapeutic use of this new class of esterified Bisphosphonates (BPs) in the treatment of tumor progression and metastasis without toxic adverse effects

Nanomagnetic-Supported Catalysts

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One-pot C-C coupling and nitro-reduction in aqueous media using a nanocatalyst

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One-pot Suzuki/Sonogashira and nitro-reduction in aqueous media using a magnetic nanocatalyst

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Magneto-Optic Effects in Doped InP

ABSTRACTIron oxide nanoparticles (NPs) have attracted a lot of interest due to their many potential applications in areas including optoelectronics, magneto-optics, high density data storage, etc. In particular, iron oxides (Fe3O4 and γ –Fe2O3) are also well suited for biomedical applications [1]. We have investigated Faraday Rotation (FR) response for two types of Fe2O3 NPs (in aqueous suspension) that are of the same average diameter (10 nm) but differ in one important respect; one group consists of uncoated particles whereas the other group is functionalized with caffeic acid. This system is being investigated and characterized for use in tumor imaging applications. Faraday rotation (FR) refers to the rotation of the polarization vector of a light beam as it passes through a sample in the presence of a magnetic field. FR can reveal interesting material properties such as saturation magnetization and wavelength dependent Verdet constant of the material under investigation. The latter is a measure of the magnetically induced birefringence of the material. Typically FR setups rely on AC or DC magnetic fields. While these are valuable techniques with their own advantages, this work focuses on a pulsed field setup that can reveal dynamic information about the resulting magnetization, as the magnetic response of the sample is measured in the presence of short intense fields on the order of 0.6 Tesla and lasting approximately 100 milliseconds. All experiments are carried out at excitation wavelength of 633 nm (He-Ne wavelength).The two NP samples show very different response to the field pulses. The NP systems investigated in this work show very unique short term and long term behavior revealing various time scales of interest. These unique characteristic times for the functionalized vs. uncoated particles provide valuable clues about the magnetization response of the NP and its relationship to the detailed structure of the NPs (core vs. shell). Magnetic response from these systems persists long after the magnetic field pulse has subsided. This can be related to the relaxation modes (Néel vs. Brownian) and as possible evidence of NP size dispersion. Additionally, the possibility of agglomeration is also discussed. While more detailed quantitative analysis will be dealt with in a more comprehensive publication that is under preparation, we hope to show in this preliminary report both that the AC and pulsed FR measurements can reveal complimentary information and that FR in general can be a reliable technique, which can be used to develop a detailed picture of the magnetic response of these NP systems.</jats:p

Bivalent alkyne-bisphosphonate as clickable and solid anchor to elaborate multifunctional iron oxide nanoparticles with microwave enhancement

International audienceWe report the elaboration of clickable superparamagnetic nanoparticles that act as a scaffold for further modifications by click chemistry. This nano platform is easily obtained by coating iron oxide nanoparticle γ-Fe2O3, with a new bifunctional molecule (1-hydroxy-1-phosphonopent-4-ynyl)phosphonic acid (HMBPyne). The HMBP and the alkyne functions act respectively as anchoring surface group and click chemistry functionality. We evaluate the functionalization of this new "clickable" nanoplateform using Huisgen 1,3-cycloaddition as model reaction and demonstrate the potential of microwave irradiation to increase the grafting yield. The effectiveness of click chemistry for the modification of mNPs is explored with a diverse array of functional species

Structure-activity relationships of a new class of aromatic bisphosphonates that inhibit tumor cell proliferation in vitro.

International audienceWe previously reported a simple and efficient one-pot procedure for synthesis of 1-hydroxymethylene-1,1-bisphosphonic acids (HMBP). According to this method, we synthesized a series of new aromatic HMBP and investigated structure-activity relationships by evaluating their anti-proliferative activity against A431 human tumor cell line. Our results showed that the introduction of an extra methylene group in a pyridyl-containing R2 side chain increased 100-fold the anti-proliferative activity of the HMBP. In contrast, this chemical modification did not modify the anti-proliferative activity of compounds substituted with a phenyl-containing R2 side chain. Para-substitution of the phenyl ring with various groups markedly influenced the HMBP activity, the order of potency (bromine > chlorine > fluorine = none) closely matching the atomic volume of the substituted group. Moreover, changes in the substitution position of the bromine group also affected the anti-proliferative activity, the more potent activity being obtained with para-substitution of the phenyl ring. In conclusion, this structure-activity study led us to identify the new aromatic HMBP [(4-Bromo-phenyl)-hydroxy-phosphono-methyl]-phosphonic acid as a potent in vitro anti-proliferative molecule against tumor cell lines (IC50 value of 9.5 x 10(-5) M). Interestingly, this compound can be further easily esterified on its phosphonic acid functions according to our chemical method and, thus, represents a potential candidate for the development of new esterified HMBP with enhanced pharmacokinetics

Solvent-Free Production by Extrusion of Bio-Based Poly(glycerol-co-diacids) Sheets for the Development of Biocompatible and Electroconductive Elastomer Composites

Faced with growing global demand for new potent, bio-based, biocompatible elastomers, the present study reports the solvent-free production of 13 pure and derived poly(glycerol-co-diacid) composite sheets exclusively using itaconic acid, sebacic acid, and 2,5-furandicarboxylic acid (FDCA) with glycerol. Herein, modified melt polycondensation and Co(II)-catalyzed polytransesterification were employed to produce all exploitable prepolymers, enabling the easy and rapid manufacturing of elastomer sheets by extrusion. Most of our samples were loaded with 4 wt% of various additives such as natural polysaccharides, synthetic polymers, and/or 25 wt% sodium chloride as porogen agents. The removal of unreacted monomers and acidic short oligomers was carried out by means of washing with NaHCO3 aqueous solution, and pH monitoring was conducted until efficient sheet surface neutralization. For each sheet, their surface morphologies were observed by Field-emission microscopy, and DSC was used to confirm their amorphous nature and the impact of the introduction of every additive. The chemical constitution of the materials was monitored by FTIR. Then, cytotoxicity tests were performed for six of our most promising candidates. Finally, we achieved the production of two different types of extrusion-made PGS elastomers loaded with 10 wt% PANI particulates and 4 wt% microcrystalline cellulose for adding potential electroconductivity and stability to the material, respectively. In a preliminary experiment, we showed the effectiveness of these materials as performant, time-dependent electric pH sensors when immersed in a persistent HCl atmosphere

η 1 −η 2 Rearrangement and Protonation of Phenyldiazo Bridging Ligands Attached to the Dimolybdenum System {Mo 2 Cp 2 (μ-SMe) 3 }

International audienceRearrangements and protonation reactions of phenyldiazo ligands bound to the bimetallic center, {Mo2Cp2(μ-SMe)3}, are reporte