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691.
Canistro D Melega S Ranieri D Sapone A Gustavino B Monfrinotti M Rizzoni M Paolini M 《Mutation research》2012,729(1-2):81-89
Epidemiological studies have shown an association between consumption of disinfected drinking water and adverse health outcomes. The chemicals used to disinfect water react with occurring organic matter and anthropogenic contaminants in the source water, resulting in the formation of disinfection by-products (DBPs). The observations that some DBPs are carcinogenic in animal models have raised public concern over the possible adverse health effects for humans. Here, the modulation of liver cytochrome P450-linked monooxygenases (MFO) and the genotoxic effects in erythrocytes of Cyprinus carpio fish exposed in situ to surface drinking water in the presence of disinfectants, such as sodium hypochlorite (NaClO), chlorine dioxide (ClO(2)) and peracetic acid (PAA), were investigated in winter and summer. A complex induction/suppression pattern of CYP-associated MFOs in winter was observed for all disinfectants. For example, a 3.4- to 15-fold increase was recorded of the CYP2B1/2-linked dealkylation of penthoxyresorufin with NaClO (10 days) and PAA (20 days). In contrast, ClO(2) generated the most notable inactivation, the CYP2E1-supported hydroxylation of p-nitrophenol being decreased up to 71% after 10 days' treatment. In summer, the degree of modulation was modest, with the exception of CYP3A1/2 and CYP1A1 supported MFOs (62% loss after 20 days PAA). The micronucleus (MN) induction in fish circulating erythrocytes was also analysed as an endpoint of genotoxic potential in the same fish population. Significant increases of MN induction were detected at the latest sampling time on fish exposed to surface water treated with chlorinate-disinfectants, both in winter (NaClO) and summer (NaClO and ClO(2)), while no effect was observed in fish exposed to PAA-treated water. These results show that water disinfection may be responsible for harmful outcomes in terms of MFO perturbation and DNA damage; if extrapolated to humans, they ultimately offer a possible rationale for the increased urinary cancer risk recorded in regular drinking water consumers. 相似文献
692.
N Vaiana M Marzahn S Parapini P Liu M Dell'agli A Pancotti E Sangiovanni N Basilico E Bosisio BM Dunn D Taramelli S Romeo 《Bioorganic & medicinal chemistry letters》2012,22(18):5915-5918
We report the discovery of new potent inhibitors of the growth of Plasmodium falciparum chloroquine (CQ)-resistant W2 strain. These compounds were designed using the double drug approach by introducing a residue able to enhance the accumulation of plasmepsins inhibitors into the food vacuole. Some of the molecules were more active than CQ against CQ-resistant strain and showed good selectivity against cathepsin D. 相似文献
693.
Manolo Casagrande Anna Barteselli Nicoletta Basilico Silvia Parapini Donatella Taramelli Anna Sparatore 《Bioorganic & medicinal chemistry》2012,20(19):5965-5979
With the aim to investigate the effect of different heterocyclic rings linked to the 4-aminoquinoline nucleus on the antimalarial activity, a set of 7-chloro-N-(heteroaryl)-methyl-4-aminoquinoline and 7-chloro-N-(heteroaryl)-4-aminoquinoline was synthesized and tested in vitro against D-10 (CQ-S) and W-2 (CQ-R) strains of Plasmodium falciparum. All compounds exhibited from moderate to high antiplasmodial activities. The activity was strongly influenced both by the presence of a methylenic group, as a spacer between the 4-aminoquinoline and the heterocyclic ring, and by the presence of a basic head. The most potent molecules inhibited the growth of both CQ-S and CQ-R strains of P. falciparum with IC50 < 30 nM and were not toxic against human endothelial cells. These results confirm that the presence of an heteroaryl moiety in the side chain of 7-chloro-4-aminoquinoline is useful for the design and development of new powerful antimalarial agents. 相似文献
694.
Leonardo Manzoni Laura Belvisi Aldo Bianchi Annalisa Conti Carmelo Drago Marilenia de Matteo Luca Ferrante Eloise Mastrangelo Paola Perego Donatella Potenza Carlo Scolastico Federica Servida Gabriele Timpano Francesca Vasile Vincenzo Rizzo Pierfausto Seneci 《Bioorganic & medicinal chemistry》2012,20(22):6687-6708
Novel pro-apoptotic, homo- and heterodimeric Smac mimetics/IAPs inhibitors based on the N-AVPI-like 4-substituted 1-aza-2-oxobicyclo[5.3.0]decane scaffold were prepared from monomeric structures connected through a head–head (8), tail–tail (9) or head–tail (10) linker. The selection of appropriate decorating functions for the scaffolds, and of rigid and flexible linkers connecting them, is described. The synthesis, purification and analytical characterization of each prepared dimer 8–10 is thoroughly described. 相似文献
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697.
Feniouk BA Rebecchi A Giovannini D Anefors S Mulkidjanian AY Junge W Turina P Melandri BA 《Biochimica et biophysica acta》2007,1767(11):1319-1330
H(+)-F(O)F(1)-ATP synthase couples proton flow through its membrane portion, F(O), to the synthesis of ATP in its headpiece, F(1). Upon reversal of the reaction the enzyme functions as a proton pumping ATPase. Even in the simplest bacterial enzyme the ATPase activity is regulated by several mechanisms, involving inhibition by MgADP, conformational transitions of the epsilon subunit, and activation by protonmotive force. Here we report that the Met23Lys mutation in the gamma subunit of the Rhodobacter capsulatus ATP synthase significantly impaired the activation of ATP hydrolysis by protonmotive force. The impairment in the mutant was due to faster enzyme deactivation that was particularly evident at low ATP/ADP ratio. We suggest that the electrostatic interaction of the introduced gammaLys23 with the DELSEED region of subunit beta stabilized the ADP-inhibited state of the enzyme by hindering the rotation of subunit gamma rotation which is necessary for the activation. 相似文献
698.
An interference free amperometric biosensor for the detection of biogenic amines in food products 总被引:2,自引:0,他引:2
In this work is reported the development and application of an amperometric biosensor for the determination of total biogenic amines content by using the commercial diamino oxidase (DAO from Porcine kidney E.C. 1.4.3.6) as the biocomponent, entrapped by glutaraldehyde onto an electrosynthesized bilayer film. In order to minimize both the fouling and the interference caused by the direct electrochemical oxidation of both the analytes (i.e., biogenic amines) and the common interferents usually present in food products the performances of Pt and Au electrodes and of several electroproduced anti-interferents mono- and bi-layer films were tested. In spite of a very low activity of the commercial DAO, the biosensor displayed a high response sensitivity in flow experiments, short response time, a good linear response and low detection limits. The excellent anti-interference characteristics allowed the use of the biosensor in screening analysis of food products. 相似文献
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