1,721,117 research outputs found
Metal-based antitumour drugs in the post genomic era
No full textThe discovery of new metal-based antitumour drugs, whether cisplatin derivatives or those based on
other metals, has been largely based on cell viability assays (IC50 values) and compounds that bind to
DNA. This approach has been applied for more than 30 years during which time very few new drugs
have entered clinical use. In this article we discuss what the future holds for metal-based drugs, in
particular anti-metastasis drugs, in these enlightened times of the post genomic era
Styrene oxidation by hydrogen peroxide in ionic liquids: the role of the solvent on the competition between two Pd-catalyzed processes, oxidation and dimerization
No full textA series of hydrophilic N,N-dimethylpyrrolidinium-and N,N-dimethylpiperidinium-based ionic liquids (ILs) have been prepared and applied as reaction media in the Wacker oxidation of styrene by hydrogen peroxide using PdCl(2) as the catalyst. The efficiency of these ILs was compared with hydrophilic and hydrophobic imidazolium systems (including those with nitrile functionalities). The nature of the ionic liquid strongly influences the product distribution. In particular, in hydrophobic ILs, relevant amounts of 1,3-diphenyl-1-butene arising from styrene dimerization were detected, in addition to the expected phenylmethylketone. The formation of 1,3-diphenyl-1-butene may be attributed to the formation of Pd(0) species from "ClPdOH" (probably formed during the Wacker process) in a side-reaction. Consequently, the ability of the IL to favor or disfavor the reoxidation of "ClPdOH" to "ClPdOOH" by hydrogen peroxide, giving an homogeneous phase or a biphasic system, appears to be the main factor affecting selectivity
The role of cisplatin and NAMI-A plasma-protein interactions in relation to combination therapy
No full textModulation of the metastatic progression of breast cancer with an organometallic ruthenium compound
No full textPreclinical combination therapy of the investigational drug NAMI-A with doxorubicin for mammary cancer
No full textAIM OF THE STUDY: The tumor metastases targeting ruthenium complex NAMI-A synergistically improves the activity of gemcitabine in combination therapies. High-throughput screening was used to identify other potential drug combinations from a library of FDA approved drugs. Doxorubicin was identified as a hit compound and was therefore evaluated in combination with NAMI-A in vitro and in a preclinical in vivo model.
RESULTS: High-throughput screening identified eight structurally diverse compounds that synergize with NAMI-A including doxorubicin. The combination index on MCF-7 cells showed synergism as the concentration of NAMI-A increases independent of the doxorubicin concentration. In MCa mammary carcinoma of CBA mice, NAMI-A (35 mg/kg/day i.p. on days 7-12) followed by doxorubicin (10 mg/kg i.p. on day 16), significantly increased the effects of the individual drugs on metastases with 70 % animals resulting free of macroscopically detectable tumor nodules in the lungs at sacrifice. NAMI-A, unlike doxorubicin, cured 60 % of the treated mice but the combination therapy was toxic to the animals.
CONCLUSIONS: The combined therapy of NAMI-A with doxorubicin synergizes on lung metastasis in a preclinical mouse model. The combination therapy at the maximum tolerated doses of the two drugs is toxic. Hence, this combination is not suitable for clinical studies using maximum tolerated doses
Remarkable anion and cation effects on Stille reactions in functionalised ionic liquids
No full textTask-specific ionic liquids bearing nitrile functional groups attached to the cation and nitrogen-donor-containing anions strongly affect the efficiency of the Stille cross-coupling, influencing, the nature of the catalyst and its stability. The relative strengths of the coordinating power of the cations and anions are varied and compared, and under certain conditions nanoparticles are observed
SYNTHESIS, MOLECULAR AND CRYSTAL-STRUCTURES OF ARENE DERIVATIVES OF [RU6C(CO)17]
No full textThe complexes [Ru6C(CO)14(eta6-C6H4Me2-1,3)] 1, [Ru6C(CO)14(eta6CH3Et3-1,3,5)] 2 and [Ru6C-(CO)14(mu3-eta2:eta2:eta2-C16H16)] 3 have been prepared from the reaction of [Ru3(CO)12] and the appropriate arene. The molecular and crystal structures of the three derivatives have been established by single-crystal X-ray diffraction studies. Complexes 1 and 2 carry the arene fragment bound in a terminal fashion. Crystalline 1 contains two independent molecules showing different rotameric conformations of the xylene ligands. The [2.2]paracyclophane complex 3 provides the first example of a mono(arene) derivative of [Ru6C(CO)17] to contain the mu3-eta2:eta2:eta2-bonding mode. The molecular organization in the crystal structures of 1, 2 and 3 was also determined
HEXANUCLEAR ARENE CLUSTERS OF RUTHENIUM
No full textThe hexanuclear cluster (Ru6C(CO)14(eta6-arene)] 1 (arene = C6H6, C6H5Me, C6H4Me2-1,3 or C6H3Me3-1,3,5) reacts with Me3NO-CH2Cl2 in the presence of cyclohexa-1,3-diene or cyclohexa-1,4-diene to yield compound [Ru6C(CO)12(eta6-arene)(mu-eta2:eta2-C6H8)] 2 in which the diene spans one metal edge of the octahedral cluster unit. Further treatment of 2 with Me3NO-CH2Cl2 affords the bis(arene) derivative [Ru6C(CO)11(eta6-arene)(C6H6)]. Onthe basisof spectroscopic data and single-crystal X-raydata itappears that these bis(arene) derivatives exist in two isomeric forms, viz. [Ru6C(CO)11(eta6-arene)(mu-eta2:eta2:eta2-C6H6)] 3 and (Ru6C(CO)11(eta6-arene)(eta6-C6H6)] 4. Evidence that compound 3 isformed initially,followed by isomerisation to 4 is presented. The structures of [Ru6C(CO)11(eta6-C6H5Me)(mu3-eta2:eta2:eta2-C6H6)] 3b and [Ru6C(CO)11(eta6-C6H4Me2-1,3)(mu3-eta2:eta2:eta2-C6H6)] 3c have been determined by single-crystal X-ray diffraction. Compound 3b is orthorhombic. space group Pnma, a = 9.035(5), b = 14.796(2), c = 20.534(4) angstrom, Z = 4, 1770 unique observed reflections [I > 2sigma(I)], R = 0.020; 3c is monoclinic, space group P2(1)/n, a = 18.27(2), b = 9.729(2), c = 34.39(3) angstrom, beta = 94.94(6)-degrees, Z = 8, 7833 unique observed reflections [I > 2.0sigma(I)], R = 0.058, R' = 0.062
Development of nitrile-functionalized ionic liquids for C-C coupling reactions: Implication of carbene and nanoparticle catalysts
No full textA series of nitrile-functionalized imidazolium salts (many of which are liquid at room temperature) have been prepared. The reactivity of these salts with PdCl(2) has been studied, resulting in salts containing a tetrachloropalladate dianion or compounds in which the nitrile substituent coordinates to the palladium center. Further derivation of the latter compounds affords carbenes. All the new compounds have been characterized by spectroscopic methods and nine of them by single-crystal X-ray diffraction. The catalytic activity of the different palladium salts in Suzuki, Stille, and Heck reactions has been evaluated in some of the nitrile-functionalized ionic liquids (ILs) and compared with that of nonfunctionalized ILs, providing insights into the nature of the actual catalyst. In some instances, palladium nanoparticles have been identified, but the nature of the catalyst strongly depends on the IL employed
SYNTHESIS AND CRYSTALLOGRAPHIC CHARACTERIZATION OF [RU7C(CO)(16)(C9H8)] AND [RU7C(CO)(16)(C12H12)] - FACIAL PI-BONDING AND SIGMA BONDING FROM THE SAME RING-SYSTEM
No full textThe heptanuclear clusters [Ru7C(CO)(16)(C9H8)] and [Ru7C(CO)(16)(C12H12)] have been isolated from the reaction between [Ru-3(CO)(12)] and isopropenyl- or 1,3-diisopropenyl-benzene and their crystal structures determined: the Ru-7 cores represent rare examples of spiked octahedra; the organo-ligands are bound through all four pi bonds to a metal face and through two sigma bonds to the ruthenium spike, donating a total of ten electrons
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