Malaria afflicts about 500 million people worldwide thus causing significant global economic toll. The drugs available to treat the disease are rapidly losing their efficacy because of widespread prevalence of drug resistant parasites. Thus there is an urgent need to discover novel malaria therapeutics. This research is focused on to study the properties of a novel naturallike synthetic scaffold and analyze its selectivity, and cellular mechanism of action in Plasmodium falciparum. We have identified a novel compound, 3-amino-2-piperidinequinoline (APQ), which we termed UCF401. APQ demonstrated IC[sub50] at submicromolar concentrations against Plasmodium falciparum using the SYBR Green-I fluorescence assay measuring cellular proliferation. This compound also demonstrated low cytotoxicity against the NIH3T3 and HEPG2 cells using MTS assays, showing an IC50 of 174 [micro]M and 125 [micro]M respectively, suggesting of excellent selectivity. We evaluated the compliance of APQ with Lipinski's parameters and determined the in vitro physicochemical profiles of the compound. Our results show that APQ is a Lipinski parameter compliant and has good physicochemical properties. The cellular mechanism of action of APQ was characterized through the assessment of the effects of the compound at different stages of the parasite's intraerythrocytic life cycle. This assay was done by treating a synchronized cell line with the compound at 5X the IC50 value and then imaging the cells at 12-hour intervals. We found that APQ arrests parasite development at the trophozoite stage. In addition we determined that APQ is parasitocidal after a 96 h exposure. These results demonstrate that APQ can be considered as a validated hit and/or early lead.

Submitted by Silvana Teresinha Dornelles Studzinski (sstudzinski) on 2016-02-15T11:15:11Z No. of bitstreams: 1 Maria Cristina Vieweger de Mattos_.pdf: 602543 bytes, checksum: bbb5b1e93f88bc5d40ecb8e53b99d3be (MD5) / Made available in DSpace on 2016-02-15T11:15:11Z (GMT). No. of bitstreams: 1 Maria Cristina Vieweger de Mattos_.pdf: 602543 bytes, checksum: bbb5b1e93f88bc5d40ecb8e53b99d3be (MD5) Previous issue date: 2015-08-31 / Nenhuma / A pesquisa em psicoterapia tem ampliado o estudo do abandono terapêutico através da exploração das variáveis do processo, incluindo variáveis do paciente, do terapeuta e da interação. Poucos estudos direcionam suas investigações para a adolescência, principalmente, para a descrição dos processos e dos resultados terapêuticos. Contudo, a adaptação de instrumentos que consideram as peculiaridades da adolescência é uma área importante a ser investida. Nesse sentido, esta dissertação de mestrado teve como principal objetivo avaliar o processo psicoterápico de uma adolescente em que o desfecho clínico foi o abandono. Para tal, as sessões foram codificadas com um instrumento da metodologia Q-sort adaptado para adolescência. O Adolescent Psychotherapy Q-Set (APQ) visa avaliar sessões de psicoterapia através de 100 itens que descrevem o terapeuta, as atitudes e os comportamentos do paciente, bem como as interações terapeuta/paciente. Foram selecionados para descrever o processo os itens mais e menos característicos da psicoterapia. Essa consistiu de duas etapas de tratamento: 12 sessões e um abandono, retorno após 2 meses de afastamento e 8 sessões que culminaram em mais um abandono. Através de análises e narrativas descritivas das sessões, foram analisadas as variáveis da paciente, da terapeuta e da interação, buscando-se explorar o fenômeno do abandono nesta psicoterapia. Os resultados obtidos evidenciam critérios significativos a uma psicoterapia em que tanto paciente quanto terapeuta apresentaram características e posturas preditoras de uma boa aderência psicoterápica. Porém, frente ao abandono como desfecho clínico deste processo, esta dissertação aponta que a impossibilidade de aquisição de insight da paciente e a ausência de intervenções da terapeuta que visassem explorar manifestações referentes a faltas, interrupções ou pausas contribuíram para tal resultado. / Research on psychotherapy has increased the study of therapy dropout by exploiting the patient variables, therapist and theirs interaction. Few studies direct their research to adolescence, especially for the description of processes and therapeutic results. However, the adaptation of instruments that consider the peculiarities of adolescence is an important area to be invested. In this sense, this master's thesis aimed to evaluate the psychotherapeutic process of a teenage girl that the clinical outcome was the dropout. To this end, the sessions were coded with an instrument of Q-sort methodology adapted to adolescence. The Adolescent Psychotherapy Q-Set (APQ) seeks to evaluate psychotherapy sessions through 100 items describing the therapist, attitudes and behaviors of the patient and therapist-patient interactions. Was selected to describe the process, the items most and least typical of psychotherapy. This consisted of two treatment steps: twelve sessions and an dropout, returning after two months of absence and eight sessions that culminated in another dropout. Through analysis and descriptive narratives of sessions to reflect about the variables of patient, therapist and their interaction, seeking to explore the phenomenon of dropout in this psychotherapy. The results show significant criteria to psychotherapy, in which both patient and therapist showed characteristics and predictors postures to a good psychotherapeutic grip. However, against the dropout as a clinical outcome of this process, this thesis points out that the impossibility of patient's insight acquisition and the absence of therapist interventions that aimed to explore manifestations related faults, interruptions or breaks, contributed to this result.

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