952 resultados para Neutral Re(I) complexes


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The repetitive DNA sequences found at telomeres and centromeres play a crucial role in the structure and function of eukaryotic chromosomes. This role may be related to the tendency observed in many repetitive DNAs to adopt non-canonical structures. Although there is an increasing recognition of the importance of DNA quadruplexes in chromosome biology, the co-existence of different quadruplex-forming elements in the same DNA structure is still a matter of debate. Here we report the structural study of the oligonucleotide d(TCGTTTCGT) and its cyclic analog d. Both sequences form dimeric quadruplex structures consisting of a minimal i-motif capped, at both ends, by a slipped minor groove-aligned G:T:G:T tetrad. These mini i-motifs, which do not exhibit the characteristic CD spectra of other i-motif structures, can be observed at neutral pH, although they are more stable under acidic conditions. This finding is particularly relevant since these oligonucleotide sequences do not contain contiguous cytosines. Importantly, these structures resemble the loop moiety adopted by an 11-nucleotide fragment of the conserved centromeric protein B (CENP-B) box motif, which is the binding site for the CENP-B.

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Si alguna obra és de citació gairebé obligatòria quan es parla del joc, és Homo ludens, de Johan Huizinga (Huizinga, 2000). El llibre, publicat originàriament a Leiden el 1938, és la plasmació final de les reflexions dutes a terme per Huizinga des de 1903. Com fa notar el mateix autor, el seu objectiu és presentar el joc com un element omnipresent en la realitat. Tanmateix, sense compartir necessàriament la tesi del llibre (segons la qual no es pot afirmar que el joc sigui un element cultural sinó que ha d’afirmar-se que la cultura humana brolla tota ella del joc, és a dir, que la cultura mateixa ofereix el caràcter de joc i no que el joc sigui una manifestació cultural), el fet inqüestionable és que Huizinga escriu contínuament sobre les connexions entre jugar i accés a la transcendència. Aquesta correspondència serà el nostre fil conductor a fi d’establir alguns dels elements que intervenen en les complexes relacions entre autoconeixement i autotranscendència.

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This article provides an in-depth study of long-term female unemployment in Catalonia.Long-term unemployment statistics reveal which social groups are most likely to experience difficulty re-entering the labour market. In this case, we found that women are mainly affected by this type of labour exclusion, in particular poorly qualified, working-class women who are aged over 45 and with family responsibilities.The article aims to explore how the overlapping of factors such as gender, age, social class, origin and the division of work based on gender are related to long-term female unemployment. Moreover, we were able to detect which conceptual tools provide us with the production/reproduction paradigm so as to be able to analyse the future of female unemployment. The methodology we used combines quantitative and qualitative approaches. On the one hand, the analysis of secondary statistical data focusing on Catalonia is useful in understanding the situation from a macro-social perspective. On the other hand, an exploratory discussion group enables us to investigate social imaginary practises among unemployed working class women aged over 45. This discussion group was held in Igualada -capital of the Anoia region - an area of Catalonia deeply affected by unemployment in the current economic crisis.

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Introduction: The pharmaceutical aspects of drug administration in clinical trials receive poor consideration compared with the important attention devoted to the analytical and mathematical aspects of biological sample exploitation. During PK calculations, many researchers merely use for dose the nominal amount declared, overlooking the noticeable biases that may result in the assessment of PK parameters. The aim of this work was to evaluate the biases related to doses injected of a biosimilar drug in 2 Phase I clinical trials. Patients (or Materials) and Methods: In trial A, 12 healthy volunteers received different doses of a biosimilar of interferon beta-1a by either subcutaneous (SC) or intravenous (IV) injection. The doses were prepared by partially emptying 0.5-mL syringes supplied by the manufacturer (drop count procedure). In trial B, 12 healthy volunteers received 3 different formulations of the drug by IV injection (biosimilar without albumin [HSA], biosimilar with HSA and original brand [Rebif®]) and 2 different formulations as multiple SC injections (biosimilar HSA-free and original brand). In both trials, the actual dose administered was calculated as: D = C·V - losses. The product titer C was assessed by ELISA. The volume administered IV was assessed by weighting. Losses were evaluated by in vitro experiments. Finally, the binding of 125I-interferon to HSA was evaluated by counting the free and HSA complexed molecule fractions separated by gel filtration. Results: Interferon was not significantly adsorbed onto the lines used for its IV administration. In trial A, the titer was very close to the one declared (96 ± 7%). In trial B, it differed significantly (156 ± 10% for biosimilar with/without HSA and 123 ± 5% for original formulation). In trial A, the dose actually administered showed a large variability. The real injected volume could be biased up to 75% compared with the theoretical volume (for the lower dose administered [ie, 0.03 mL]). This was mainly attributed to a partial re-aspiration of the drug solution before withdrawing the syringe needle. A strict procedure was therefore applied in trial B to avoid these inaccuracies. Finally, in trial B, 125I-Interferon beta-1a binding to HSA appeared time dependent and slow, reaching 50% after 16-hour incubation, which is close to steady state reported for the comparator Rebif®. Conclusion: These practical examples (especially biases on actual titer and volume injected) illustrate that actual dose assessment deserves attention to ensure accuracy for estimates of clearance and distribution volume in the scientific literature and for registration purposes, especially for bioequivalence studies.

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Interleukin-1 receptor (IL-1RI) is a master regulator of inflammation and innate immunity. When triggered by IL-1beta, IL-1RI aggregates with IL-1R-associated protein (IL-1RAcP) and forms a membrane proximal signalosome that potently activates downstream signaling cascades. IL-1beta also rapidly triggers endocytosis of IL-1RI. Although internalization of IL-1RI significantly impacts signaling, very little is known about trafficking of IL-1RI and therefore about precisely how endocytosis modulates the overall cellular response to IL-1beta. Upon internalization, activated receptors are often sorted through endosomes and delivered to lysosomes for degradation. This is a highly regulated process that requires ubiquitination of cargo proteins as well as protein-sorting complexes that specifically recognize ubiquitinated cargo. Here, we show that IL-1beta induces ubiquitination of IL-1RI and that via these attached ubiquitin groups, IL-1RI interacts with the ubiquitin-binding protein Tollip. By using an assay to follow trafficking of IL-1RI from the cell surface to late endosomes and lysosomes, we demonstrate that Tollip is required for sorting of IL-1RI at late endosomes. In Tollip-deficient cells and cells expressing only mutated Tollip (incapable of binding IL-1RI and ubiquitin), IL-1RI accumulates on late endosomes and is not efficiently degraded. Furthermore, we show that IL-1RI interacts with Tom1, an ubiquitin-, clathrin-, and Tollip-binding protein, and that Tom1 knockdown also results in the accumulation of IL-1RI at late endosomes. Our findings suggest that Tollip functions as an endosomal adaptor linking IL-1RI, via Tom1, to the endosomal degradation machinery.

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En aquest estudi, explicaré i analitzaré aquests processos innovadors de conceptualització dels aspectes lingüístics del turisme. L'objectiu últim és explorar les possibilitats i perspectives que aquesta nova línia de treball pot obrir dins el context de l'oferta turística barcelonina, cosa que també afecta la projecció turística de Catalunya i dels Països Catalans. En termes generals, s'ha de constatar que l'ús de les llengües en activitats turístiques s'emmarca dins una política genèrica de projecció de la pròpia identitat i de promoció del patrimoni cultural. És per això que aquest treball també conté reflexions i propostes per a l'articulació del turisme cultural a Barcelona i Catalunya en base a la identitat i la cultura catalanes, amb el benentès que els termes "identitat" i "cultura" s'usen en un sentit ampli que incorpora la pròpia diversitat cultural i la producció artística contemporània al costat dels referents històrics, lingüístics i culturals que singularitzen la societat catalana.Aquest text està organitzat en tres blocs. El primer bloc tracta diverses qüestions prèvies, que ajuden a entendre els principis i conceptes que fonamenten aquest estudi, com són a) la justificació d'aquest estudi i, en definitiva, de la necessitat d'invertir en llengua i cultura en l'àmbit del turisme barceloní, que actualment lidera l'oferta de turisme cultural a Catalunya; b) el procediment que s'ha seguit per a fer l'estudi i la definició dels conceptes més importants; c) una explicació general de les connexions molt estretes que hi ha entre processos econòmics i processos sociolingüístics i que determinen la forma com les persones valoren les llengües pròpies i les dels altres en diversos àmbits socials, incloent-hi el món econòmic; i finalment, d) unes consideracions sobre el turisme cultural, això és, allò que fa que tingui sentit com a experiència d'interacció entre persones i cultures. En el segon bloc es presentaran experiències de marketització de llengües i identitats en diversos països. Em centraré bàsicament en els sectors de la publicitat i del turisme i, específicament, en les activitats que comporten l'ús de llengües no conegudes o poc conegudes pels clients. La secció sobre turisme està organitzada segons les llengües i, per al cas de les llengües cèltiques de les Illes Britàniques i per al Canadà, es subdivideix en diverses regions. Tot i que faré alguns comentaris sobre els processos de marketització de les grans llengües, em centraré en experiències associades a llengües minoritàries o políticament minoritzades. Això es justifica pel fet que les destinacions associades a grans llengües dominants dins el propi territori fins ara no s'han plantejat el rol de la llengua dins la pròpia oferta turística, excepte en allò que afecta al mercat d'ensenyament d'idiomes, aspecte sobre el qual parlaré també breument.El tercer bloc conté una valoració de conjunt sobre la trajectòria històrica de les polítiques turístiques a Barcelona i a Catalunya, amb els condicionants que poden facilitar l'articulació d'una oferta sòlida en matèria de turisme cultural. S'hi valora també la posició que ha tingut tradicionalment la llengua catalana en el món del turisme i s'elaboren propostes i línies de treball en base a les experiències analitzades al bloc 2. Veurem com, des del punt de vista sociolingüístic, les activitats turístiques plantegen reptes i oportunitats d'índole molt diversa: a) l'accés a espais o manifestacions culturals per part dels turistes i el seu impacte, b) el valor semiòtic de les llengües en la caracterització i diferenciació de productes i c) l'encaix entre les polítiques culturals i les turístiques, que pot implicar de formes complexes els diversos actors dels sectors econòmic, polític i cultural. L'estudi acaba amb un catàleg de propostes de desplegament d'una política turística basada en el patrimoni lingüístic, cultural, artístic i històric català, que ajudi a complementar i a reforçar l'oferta actual catalana, que gira principalment a l'entorn del clima i la platja.Versió en anglès del document: http://uoc.academia.edu/JoanPujolar/Papers/889133/Language_Culture_and_Tourism_Perspectives_in_Barcelona_and_Catalonia

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Els serve is de protecció a les persones en situació de dependencia configuraran I'any 2007, segons s'ha anunciat, un nou sistema d'atenció que comporta esperances pero també reptes tant a escala prestacional com de qualitat deIs serveis. Aquest article exposa els trets generals del projecte de llei estatal de "Promoció de I'autonomia personal i atenció a les persones en situació de dependencia", el contingut de I'actual sistema de serveis socials en re lació amb la tematica i les exigencies d'una veritable promoció i atenció de qualitat.

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L'étude classique des attributions de responsabilité instiguée par Heider en psychologie sociale s'est principalement bornée à aborder ce processus psychosocial dans une perspective individualiste qui se cantonne aux niveaux intra-individuel et interpersonnel (selon la distinction opérée par Doise). Les réflexions et les travaux empiriques présentés dans cette thèse ont deux objectifs. Dans un premier temps, il s?agit d'élargir cette perspective aux autres niveaux sociologique et idéologique (en faisant notamment recours à l'approche des attributions sociales et aux propositions de Fauconnet sur les règles de responsabilité). Deuxièmement, il s?agit d'éprouver la pertinence d'une telle approche dans un contexte particulier : celui du travail en groupe dont la nature des rapports sociaux qui y étaient présentés ont été manipulés à l'aide de scénarii chez des étudiant-e-s de l?Université de Lausanne. L?objectif principal de cette thèse est donc de tester un modèle d?ancrage des attributions de responsabilité qui permette de souligner les dynamiques représentationnelles sous-jacentes en termes de légitimation ou de remise en cause de l?organisation des groupes. Dans l?ensemble les résultats indiquent que si la nature des rapports sociaux (re)présentés dans un groupe sont de puissants déterminants de la manière de légitimer ou de remettre en cause l?organisation des groupes, le niveau individuel d'adhésion à des croyances idéologiques dominantes, comme la justification du système économique, représente un modérateur des prises de position des répondant-e-s interrogé-e-s. De plus, il semble que ces processus évoluent dans le temps, faisant ainsi apparaître l'existence de phénomènes de socialisation relativement plus complexes que ne le laissent entendre les recherches actuellement effectuées dans ce domaine. En effet, si des connaissances idéologiques sur le monde sont acquises dans les filières universitaires et n?interviennent pas toujours dans les processus de formation des représentations du travail en groupe, des connaissances spécifiques aux disciplines et à la politique de sélection universitaire semblent intervenir dans le processus de légitimation des rapports sociaux dans les groupes au niveau des attributions. En tentant une articulation entre les concepts d?ancrage des représentations sociales, d?attribution et de socialisation, cette thèse permet ainsi de souligner la pertinence qu?il y a à insérer une problématique en termes de croyances idéologiques dans l?étude des groupes sociaux.<br/><br/>Heider?s approach of responsibility attributions almost exclusively emphasized on an individualistic point of view ; i.e. focusing at an intraindividual and interpersonnal level of analysis according to Doise?s distinction. The reflexions and empirical studies presented here firstly aim at broaden this perspective by taking socio-structural as well as societal levels of analysis into account. Secondly, it is to test this approach in the particular domain of organized groups. Manipulation of the structure of social relations in work groups on screenplays were undertaken (in a population of students from the Lausanne University). Hence, the main goal of these studies is to test the impact of the social ancoring of social representations in the responsibility processes in terms of legitimation or opposition to the group organization. All in all, the results show that social structures are powerfull predictors of the formation of social representations of a work situation and so forth of the attribution process. Nevertheless hegemonic ideological beliefs, such as Economical System Justification, do play a substantial moderating role in this process. It also proves to be evolving through time. The present findings show that a complexe process of socialization is occuring during the student?s university life. Indeed, the results let us believe that ideological beliefs may not interact anytime in the group?s perception and in the construction of the representation of the situation. In the same time, it seems that more discipline specific oriented knowledge and the impact of selection policy at the Lausanne University also predict the groupe legimation process and interfer with the ideological beliefs. Trying to articulate concepts of fields of research like social representations, attribution and socialization, the present thesis allows to underline the heuristic potential of reabilitating ideological beliefs at a dispositional level in the study of group process.

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Microphthalmia with linear skin defects (MLS) syndrome is an X-linked male-lethal disorder also known as MIDAS (microphthalmia, dermal aplasia, and sclerocornea). Additional clinical features include neurological and cardiac abnormalities. MLS syndrome is genetically heterogeneous given that heterozygous mutations in HCCS or COX7B have been identified in MLS-affected females. Both genes encode proteins involved in the structure and function of complexes III and IV, which form the terminal segment of the mitochondrial respiratory chain (MRC). However, not all individuals with MLS syndrome carry a mutation in either HCCS or COX7B. The majority of MLS-affected females have severe skewing of X chromosome inactivation, suggesting that mutations in HCCS, COX7B, and other as-yet-unidentified X-linked gene(s) cause selective loss of cells in which the mutated X chromosome is active. By applying whole-exome sequencing and filtering for X-chromosomal variants, we identified a de novo nonsense mutation in NDUFB11 (Xp11.23) in one female individual and a heterozygous 1-bp deletion in a second individual, her asymptomatic mother, and an affected aborted fetus of the subject's mother. NDUFB11 encodes one of 30 poorly characterized supernumerary subunits of NADH:ubiquinone oxidoreductase, known as complex I (cI), the first and largest enzyme of the MRC. By shRNA-mediated NDUFB11 knockdown in HeLa cells, we demonstrate that NDUFB11 is essential for cI assembly and activity as well as cell growth and survival. These results demonstrate that X-linked genetic defects leading to the complete inactivation of complex I, III, or IV underlie MLS syndrome. Our data reveal an unexpected role of cI dysfunction in a developmental phenotype, further underscoring the existence of a group of mitochondrial diseases associated with neurocutaneous manifestations.

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Tenint en compte el temps i la energia que els mestres i professors dediquen a la correcció de redaccions i produccions escrites i el poc efecte que aquestes semblen tenir en altres produccions dels aprenents, es va dissenyar la recerca que es presenta en aquest article. Els resultats de l'estudi semblen suggerir que les correccions no faciliten l'aprenentatge. Com presentem aquesta activitat de retroalimentació a l'alumnat i la posició que li donem dins d'un enfocament basat en el procés de l'escriptura seran clau per fer que les correccions siguin facilitadores de l'aprenentatge de la producció escrita.

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Les empreses en tant que formen part de la comunitat, tenen una responsabilitat vers la mateixa i la realitat social que la forma. Les accions que es realitzen no són neutres, generant comportaments que cal saber preveure en benefici comú de totes les parts implicades directament o indirectament. Parlar de Responsabilitat Social Corporativa (RSC) ja és en si un fet positiu que dibuixa nous horitzons cap a societats més responsables i justes. L'incorporació de la RSC en el debat econòmic, social, ambiental, cultural i polític, fa preveure un recorregut llarg en el temps on cada vegada més empreses, entitats i organitzacions sumen esforços al seu voltant. El Treball Social com a professió coneixedora de la realitat social i les dificultats existents ha de poder jugar un paper proactiu en la RSC conjuntament amb d´altres actors. Des d'un treball col·laboratiu que afavoreixi espais de sinergia, on es sumin esforços per assolir una societat més humana, justa, solidària i responsable. En definitiva amb un missatge adreçat a treballar, des de diferents àmbits professionals, per garantir uns mínims de qualitat de vida per a totes les persones que formem part de la societat.

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Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin.

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Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin.

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Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin.

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The study of the reactivity of three 1-(2-dimethylaminoethyl)-1H-pyrazole derivatives of general formula [1-(CH2)2NMe2}-3,5-R2-pzol] {where pzol represents pyrazole and Rdouble bond; length as m-dashH (1a), Me (1b) or Ph (1c)} with [MCl2(DMSO)2] (Mdouble bond; length as m-dashPt or Pd) under different experimental conditions allowed us to isolate and characterize cis-[M{κ2-N,N′-{[1-(CH2)2NMe2}-3,5-R2-pzol])}Cl2] {MMdouble bond; length as m-dashPtPt (2a-2c) or Pd (3a-3c)} and two cyclometallated complexes [M{κ3-C,N,N′-{[1-(CH2)2NMe2}-3-(C5H4)-5-Ph-pzol])}Cl] {Mdouble bond; length as m-dashPt(II) (4c) or Pd(II) (5c)}. Compounds 4c and 5c arise from the orthometallation of the 3-phenyl ring of ligand 1c. Complex 2a has been further characterized by X-ray crystallography. Ligands and complexes were evaluated for their in vitro antimalarial against Plasmodium falciparum and cytotoxic activities against lung (A549) and breast (MDA MB231 and MCF7) cancer cellular lines. Complexes 2a-2c and 5c exhibited only moderate antimalarial activities against two P. falciparum strains (3D7 and W2). Interestingly, cytotoxicity assays revealed that the platinacycle 4c exhibits a higher toxicity than cisplatin in the three human cell lines and that the complex 2a presents a remarkable cytotoxicity and selectivity in lung (IC50 = 3 μM) versus breast cancer cell lines (IC50 > 20 μM). Thus, complexes 2c and 4c appear to be promising leads, creating a novel family of anticancer agents. Electrophoretic DNA migration studies in presence of the synthesized compounds have been performed, in order to get further insights into their mechanism of action.