Polymer "ruthenium-cyclopentadienyl" conjugates - New emerging anti-cancer drugs

In this work, we aimed to understand the biological activity and the mechanism of action of three polymer-'ruthenium-cyclopentadienyl' conjugates (RuPMC) and a low molecular weight parental compound (Ru1) in cancer cells. Several biological assays were performed in ovarian (A2780) and breast (MCF7, MDA-MB-231) human cancer derived cell lines as well as in A2780cis, a cisplatin resistant cancer cell line. Our results show that all compounds have high activity towards cancer cells with low IC50 values in the micromolar range. We observed that all Ru-PMC compounds are mainly found inside the cells, in contrast with the parental low molecular weight compound Ru1 that was mainly found at the membrane. All compounds induced mitochondrial alterations. PMC3 and Ru1 caused F-actin cytoskeleton morphology changes and reduced the clonogenic ability of the cells. The conjugate PMC3 induced apoptosis at low concentrations comparing to cisplatin and could overcame the platinum resistance of A2780cis cancer cells. A proteomic analysis showed that these compounds induce alterations in several cellular proteins which are related to the phenotypic disorders induced by them.Our results suggest that PMC3 is foreseen as a lead candidate to future studies and acting through a different mechanism of action than cisplatin. Here we established the potential of these Ru compounds as new metallodrugs for cancer chemotherapy.This work was financed by the Portuguese Foundation for Science and Technology (Fundacao para a Ciencia e a Tecnologia, FCT) within the scope of projects UID/QUI/00100/2013 and PTDC/QUI-QIN/28662/2017. This work was supported by the strategic program UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 - Programa Operacional Competitividade e Internacionalizacao (POCI). Andreia Valente acknowledges the COST action CM1302 (SIPs), the Investigator FCT2013 Initiative for the project IF/01302/2013 (acknowledging FCT, as well as POPH and FSE - European Social Fund) and the Royal Society of Chemistry's Research Fund. Pierre Falson and Elisabeta Comsa warmly acknowledge Thibault Andrieu from the cytometry plateau of SFR bioscience -UMS 3444- at Lyon-Gerland, France for assistance on CytoF. This work was also supported by the Marie Curie Initial Training Network: FP7-PEOPLE-2012-ITN proposal no 317297 - acronym GLYCOPHARM and PITN-GA-2012-317297. The high resolution mass spectrometer at CIRE-PAIB was financed (SMHART project no3069) by the European Regional Development Fund (ERDF), the Conseil Regional du Centre, the French National Institute for Agricultural Research (INRA) and the French National Institute of Health and Medical Research (Inserm)

Karyotype of the Cricket, Zucchiella atlantica, with an Overview of the Chromosomes of the Subfamily Nemobiinae

Few reports have been published on cytogenetics in crickets of the subfamily Nemobiinae. Within the Neotropical region the karyotypes of only two species are known, both of them belonging to the genus Phoremia. In the present paper, chromosomes of a third Neotropical species, Zucchiella atlanticaMello 1990 (Orthoptera: Trigonidiidae), have been studied and a cytological review of other species of that subfamily is presented. Zucchiella atlantica shows 2n ♂ = 22 + XO and 2n ♀ = 22 + XX which suggests an ancestral condition within the subfamily as the diploid number in all the species previously studied ranges from 2n ♂ = 7 to 2n ♀ = 21. In Orthoptera those species with high chromosome numbers tend to show reduction in their chromosomal numbers by means of centric fusions rather than to increase chromosomal numbers, due to difficulties in the availability of new centromeres. A structural polymorphism in one chromosome of pair 5 was observed as an intra-individual variation, suggesting differential activity of the genome from cell to cell

Enzymatic catalysis for bio-based polymers by step-growth polymerization

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Enzymatic catalysis for bio-based polymers by step-growth polymerization

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Synthesis and enzymatic polycondensation of new diol-diamides monomers from microalgaes

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Enzymatic catalysis for bio-based polyesters and poly(ester-co-amide)s

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Enzyme-catalyzed polycondensation of diol-diamide monomers from microalgaes : access to new poly(ester-co-amide)s

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Synthesis and enzymatic polycondensation of new diol –diamide monomers from microalgaes

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Synthesis and enzymatic polycondensation of new diol-diamides monomers from microalgaes

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