Do público e do privado: uma perspectiva de género sobre uma dicotomia moderna

Neste texto propomos uma interpretação crítica da dicotomia histórica entre público e privado como dinâmica fundamental da modernidade. A partir de uma perspectiva de género, discutimos as fronteiras construídas entre espaço coletivo de cidadania e de sociabilidade e espaço individual de intimidade e desigualdade. Argumentamos a favor de uma relação de cumplicidade, ainda que tensa, entre as duas esferas, observando que a vida privada foi, em grande medida, moldada pelas mudanças operadas na vida pública. Recorrendo a diferentes definições de "público", notamos que, à medida que as sociabilidades tradicionais, essencialmente masculinas, estudadas entre outros por Ariès ou Sennett, sofriam uma erosão, crescia o sentimento de intimidade, aumentando igualmente a inclusão do privado no público através do alargamento da cidadania, em consequência das lutas travadas na esfera pública por vários movimentos de emancipação, como o operário ou o feminista. À medida que a pessoa era retirada da comunidade, do clã, do grupo de parentesco, em que eram "naturais" as desigualdades, no sentido aristotélico do termo, ia-se reencontrando progressivamente como indivíduo portador de cidadania. Se o espaço privado se tornou central na definição de uma identidade, ele é também crescentemente atravessado por mecanismos públicos de regulação. Nesse sentido, o movimento de ascensão do privado, que nas últimas décadas tem ocupado espaço de debate, deve ser cuidadosamente reinterpretado

Inhibitors of BCRP/ABCG2 protein involved in multidrug resistance : design, synthesis and biological activity

Malgré une multitude de traitements, le cancer est aujourd’hui une maladie chronique incurable. La recherche sur le cancer a atteint un niveau de développement considérable, afin de trouver un traitement thérapeutique viable. La chimiothérapie est l’un des traitements qui est le plus utilisé et le plus général mis en place. Néanmoins, il se heurte dans près de 80 % des cas, à l’apparition de phénomènes de multirésistance (MultiDrug Resistance, MDR). Parmi les mécanismes à l’origine de la MDR, la surexpression de protéines transmembranaires de la superfamille des transporteurs ATP-Binding Cassette (ABC). Parmi elles, la protéine BCRP/ABCG2, se trouve surexprimée chez les cellules tumorales et conduit à un efflux, massif, des agents anticancéreux utilisés. Afin de resensibiliser celles-ci aux anticancéreux, notre stratégie a porté sur la conception, la synthèse et l’évaluation biologique d'inhibiteurs de BCRP/ABCG2. Ces molécules peuvent être utilisées en clinique en combinaison avec des anticancéreux. Ces inhibiteurs s’appuient sur le chef de file, le MBL-II-141, le meilleur inhibiteur in vitro et in vivo de la protéine à ce jour et, développé au laboratoire.Cancer is a major chronic disease for which no curative treatment is available. Despite the number of anticancer drugs available, resistance of tumours to multiple structurally-unrelated anticancer drugs is a common clinical problem that limits the curative potential of chemotherapy in clinical oncology. Treatments are very invasive for the patients, especially those suffering of recurrence. Eradication of resistant cells in tumours would then have a considerable impact for curing cancer by chemotherapy. This resistance is often due to overexpression of three major multidrug ABC efflux pumps including Breast Cancer Resistance Protein (BCRP/ABCG2) which confer a multidrug-resistance (MDR) phenotype. In order to restore the sensibility of tumor cells toward anticancer drugs, one strategy would be the development of inhibitors of BCRP/ABCG2 to be used in adjuvants with clinically used anticancer drugs. Hence, our work was focused on the design, synthesis and biological evaluation of specific inhibitors of BCRP/ABCG2 based on the pharmacomodulation of MBL-II-141, an in vivo effective inhibitor, previously developed in our laboratory

Chromones bearing amino acid residues: Easily accessible and potent inhibitors of the breast cancer resistance protein ABCG2

International audienceThe Breast Cancer Resistance Protein (BCRP/ABCG2) belongs to the G class of ABC (ATP-Binding Cassette)proteins, which is known as one of the main transporters involved in the multidrug resistance (MDR)phenotype that confer resistance to anticancer drugs. The aim of this study was to design, synthesize anddevelop new potent and selective inhibitors of BCRP that can be used to abolish MDR and potentializeclinically used anticancer agents. In previous reports, we showed the importance of chromone scaffoldand hydrophobicity for the inhibition of ABC transporters. In the present study we report the design anddevelopment of chromones linked to one or two amino acids residues that are either hydrophobic orfound in the structure of FTC, one of most potent (but highly toxic) inhibitors of BCRP. Herewith, wereport the synthesis and evaluation of 13 compounds. The studied molecules were found to be not toxicand showed strong inhibition activity as well as high selectivity toward BCRP. The highest activity wasobtained with the chromone bearing a valine residue (9c) which showed an inhibition activity againstBCRP of 50 nM. The rationalization of the inhibition potential of the most active derivatives was performedthrough docking studies. Taken together, the ease of synthesis and the biological profile of thesecompounds render them as promising candidates for further development in the field of anticancertherapy

Inhibitors of ABCG2-mediated multidrug resistance: Lead generation through computer-aided drug design

International audienceHuman breast cancer resistance protein (BCRP), known also as ABCG2, plays a major role in multiple drug resistance (MDR) in tumor cells. Through this ABC transporter, cancer cells acquire the ability of resistance to structurally and functionally unrelated anticancer drugs. Nowadays, the design of ABCG2 inhibitors as potential agents to enhance the chemotherapy efficacy is an interesting strategy. In this context, we have used computer-aided drug design (CADD) based on available data of a large series of potent inhibitors from our groups as an approach in guiding the design of effective ABCG2 inhibitors. We report therein the results on the use of the FLAPpharm method to elucidate the pharmacophoric features of one of the ABCG2 binding sites involved in the regulation of the basal ATPase activity of the transporter. The predictivity of the model was evaluated by testing three predicted compounds which were found to induce high inhibitory activity of BCRP, in the nanomolar range for the best of them

Optimization of the chromone scaffold through QSAR and docking studies: Identification of potent inhibitors of ABCG2

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