18 research outputs found

    Rhodium(III) dihalido complexes: The effect of ligand substitution and halido coordination on increasing cancer cell potency

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    This work presents the synthesis of eight new rhodium(III) dihalido complexes, [RhX2(L)(LH)] (where X = Cl or I), which incorporate two bidentate N-(3-halidophenyl)picolinamide ligands. The ligands have different binding modes in the complexes, whereby one is neutral and bound via N,N (LH) coordination, while the other is anionic and bound via N,O (L) coordination. The solid state and solution studies confirm multiple isomers are present when X = Cl; however, after a halide exchange with potassium iodide (X = I) the complexes exist exclusively as single stable trans isomers. NMR studies reveal the Rh(III) trans diiodido complexes remain stable in aqueous solution with no ligand exchange reported over 96 h. Chemosensitivity data against a range of cancer cell lines show two cytotoxic complexes, where L = N-(3-bromophenyl)picolinamide ligand. The results have been compared to the analogous Ru(III) complexes and overall highlight the Rh(III) trans diiodido complex to be ∌78× more cytotoxic than the analogous Rh(III) dichlorido complex, unlike the Ru(III) complexes which are equitoxic against all cell lines. Additionally, the Rh(III) trans diiodido complex is more selective toward cancerous cells, with selectivity index (SI) values >25-fold higher than cisplatin against colorectal carcinoma

    The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis

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    Background A growing body of research identifies the harmful effects that adverse childhood experiences (ACEs; occurring during childhood or adolescence; eg, child maltreatment or exposure to domestic violence) have on health throughout life. Studies have quantified such effects for individual ACEs. However, ACEs frequently co-occur and no synthesis of findings from studies measuring the effect of multiple ACE types has been done. Methods In this systematic review and meta-analysis, we searched five electronic databases for cross-sectional, case-control, or cohort studies published up to May 6, 2016, reporting risks of health outcomes, consisting of substance use, sexual health, mental health, weight and physical exercise, violence, and physical health status and conditions, associated with multiple ACEs. We selected articles that presented risk estimates for individuals with at least four ACEs compared with those with none for outcomes with sufficient data for meta-analysis (at least four populations). Included studies also focused on adults aged at least 18 years with a sample size of at least 100. We excluded studies based on high-risk or clinical populations. We extracted data from published reports. We calculated pooled odds ratios (ORs) using a random-effects model. Findings Of 11 621 references identified by the search, 37 included studies provided risk estimates for 23 outcomes, with a total of 253 719 participants. Individuals with at least four ACEs were at increased risk of all health outcomes compared with individuals with no ACEs. Associations were weak or modest for physical inactivity, overweight or obesity, and diabetes (ORs of less than two); moderate for smoking, heavy alcohol use, poor self-rated health, cancer, heart disease, and respiratory disease (ORs of two to three), strong for sexual risk taking, mental ill health, and problematic alcohol use (ORs of more than three to six), and strongest for problematic drug use and interpersonal and self-directed violence (ORs of more than seven). We identified considerable heterogeneity (I 2 of > 75%) between estimates for almost half of the outcomes. Interpretation To have multiple ACEs is a major risk factor for many health conditions. The outcomes most strongly associated with multiple ACEs represent ACE risks for the next generation (eg, violence, mental illness, and substance use). To sustain improvements in public health requires a shift in focus to include prevention of ACEs, resilience building, and ACE-informed service provision. The Sustainable Development Goals provide a global platform to reduce ACEs and their life-course effect on health. Funding Public Health Wales. © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licens

    Structure–activity relationships for organometallic osmium arene phenylazopyridine complexes with potent anticancer activity

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    We report the synthesis and characterisation of 32 half sandwich phenylazopyridine Os(II) arene complexes [Os(eta(6)-arene)(phenylazopyridine)X](+) in which X is chloride or iodide, the arene is p-cymene or biphenyl and the pyridine and phenyl rings contain a variety of substituents (F, Cl, Br, I, CF(3), OH or NO(2)). Ten X-ray crystal structures have been determined. Cytotoxicity towards A2780 human ovarian cancer cells ranges from high potency at nanomolar concentrations to inactivity. In general the introduction of an electron-withdrawing group (e.g. F, Cl, Br or I) at specific positions on the pyridine ring significantly increases cytotoxic activity and aqueous solubility. Changing the arene from p-cymene to biphenyl and the monodentate ligand X from chloride to iodide also increases the activity significantly. Activation by hydrolysis and DNA binding appears not to be the major mechanism of action since both the highly active complex [Os(eta(6)-bip)(2-F-azpy)I]PF(6) (9) and the moderately active complex [Os(eta(6)-bip)(3-Cl-azpy)I]PF(6) (23) are very stable and inert towards aquation. Studies of octanol-water partition coefficients (log P) and subcellular distributions of osmium in A2780 human ovarian cancer cells suggested that cell uptake and targeting to cellular organelles play important roles in determining activity. Although complex 9 induced the production of reactive oxygen species (ROS) in A2780 cells, the ROS level did not appear to play a role in the mechanism of anticancer activity. This class of organometallic osmium complexes has new and unusual features worthy of further exploration for the design of novel anticancer drugs

    Rhodium, Iridium, and Ruthenium Half-Sandwich Picolinamide Complexes as Anticancer Agents

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    Novel rhodium, iridium, and ruthenium half-sandwich complexes containing (<i>N</i>,<i>N</i>)-bound picolinamide ligands have been prepared for use as anticancer agents. The complexes show promising cytotoxicities, with the presence, position, and number of halides having a significant effect on the corresponding IC<sub>50</sub> values. One ruthenium complex was found to be more cytotoxic than cisplatin on HT-29 and MCF-7 cells after 5 days and 1 h, respectively, and it remains active with MCF-7 cells even under hypoxic conditions, making it a promising candidate for <i>in vivo</i> studies

    Rhodium, Iridium, and Ruthenium Half-Sandwich Picolinamide Complexes as Anticancer Agents

    No full text
    Novel rhodium, iridium, and ruthenium half-sandwich complexes containing (<i>N</i>,<i>N</i>)-bound picolinamide ligands have been prepared for use as anticancer agents. The complexes show promising cytotoxicities, with the presence, position, and number of halides having a significant effect on the corresponding IC<sub>50</sub> values. One ruthenium complex was found to be more cytotoxic than cisplatin on HT-29 and MCF-7 cells after 5 days and 1 h, respectively, and it remains active with MCF-7 cells even under hypoxic conditions, making it a promising candidate for <i>in vivo</i> studies

    Rhodium, Iridium, and Ruthenium Half-Sandwich Picolinamide Complexes as Anticancer Agents

    No full text
    Novel rhodium, iridium, and ruthenium half-sandwich complexes containing (<i>N</i>,<i>N</i>)-bound picolinamide ligands have been prepared for use as anticancer agents. The complexes show promising cytotoxicities, with the presence, position, and number of halides having a significant effect on the corresponding IC<sub>50</sub> values. One ruthenium complex was found to be more cytotoxic than cisplatin on HT-29 and MCF-7 cells after 5 days and 1 h, respectively, and it remains active with MCF-7 cells even under hypoxic conditions, making it a promising candidate for <i>in vivo</i> studies

    Rhodium, Iridium, and Ruthenium Half-Sandwich Picolinamide Complexes as Anticancer Agents

    No full text
    Novel rhodium, iridium, and ruthenium half-sandwich complexes containing (<i>N</i>,<i>N</i>)-bound picolinamide ligands have been prepared for use as anticancer agents. The complexes show promising cytotoxicities, with the presence, position, and number of halides having a significant effect on the corresponding IC<sub>50</sub> values. One ruthenium complex was found to be more cytotoxic than cisplatin on HT-29 and MCF-7 cells after 5 days and 1 h, respectively, and it remains active with MCF-7 cells even under hypoxic conditions, making it a promising candidate for <i>in vivo</i> studies

    Rhodium, Iridium, and Ruthenium Half-Sandwich Picolinamide Complexes as Anticancer Agents

    No full text
    Novel rhodium, iridium, and ruthenium half-sandwich complexes containing (<i>N</i>,<i>N</i>)-bound picolinamide ligands have been prepared for use as anticancer agents. The complexes show promising cytotoxicities, with the presence, position, and number of halides having a significant effect on the corresponding IC<sub>50</sub> values. One ruthenium complex was found to be more cytotoxic than cisplatin on HT-29 and MCF-7 cells after 5 days and 1 h, respectively, and it remains active with MCF-7 cells even under hypoxic conditions, making it a promising candidate for <i>in vivo</i> studies

    Rhodium, Iridium, and Ruthenium Half-Sandwich Picolinamide Complexes as Anticancer Agents

    No full text
    Novel rhodium, iridium, and ruthenium half-sandwich complexes containing (N,N)-bound picolinamide ligands have been prepared for use as anticancer agents. The complexes show promising cytotoxicities, with the presence, position, and number of halides having a significant effect on the corresponding IC50 values. One ruthenium complex was found to be more cytotoxic than cisplatin on HT-29 and MCF-7 cells after 5 days and 1 h, respectively, and it remains active with MCF-7 cells even under hypoxic conditions, making it a promising candidate for in vivo studies
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