Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-04-25T12:54:42Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação Andrade, Fabricio Havy Dantas de.pdf: 3417909 bytes, checksum: eef7f131646ef614d1e9a858a3bef036 (MD5) / Made available in DSpace on 2017-04-25T12:54:42Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação Andrade, Fabricio Havy Dantas de.pdf: 3417909 bytes, checksum: eef7f131646ef614d1e9a858a3bef036 (MD5) Previous issue date: 2016-02-16 / FACEPE / CAPES / O 3-(2,6-diflúor-benzil)-5-(5-bromo-1H-indol-3-ilmetileno)-tiazolidina-2,4-diona (LPSF/GQ-238) é um análogo indólico-tiazolidínico, apresenta potencial atividade esquistossomicida e tripanossomicida. Poucos relatos na literatura mostram a eficácia de uma substância contra a esquistossomose e a doença de chagas. Estas doenças são consideradas doenças debilitantes e afeta milhões de pessoas no mundo. Assim, o objetivo deste trabalho foi realizar a caracterização físico-química do LPSF/GQ-238 visando conhecer suas propriedades químicas e físicas para desenvolvimento de uma nova alternativa de tratamento para as doenças supracitadas. O estudo abrangeu a caracterização físico-química, estabilidade térmica e compatibilidade fármaco-excipiente por técnicas espectroscópicas (IV, RMN), termoanalíticas (DSC, DSC-fotovisual, TG e Pyr-CG/EM), validação do método analítico, bem como DRX e MEV. Os resultados obtidos da avaliação físicoquímica do LPSF/GQ-238 frente a diferentes técnicas permitiram caracterizá-lo do ponto de vista físico, químico e morfológico. O protótipo apresentou-se com 99,5% de pureza, funde a 272,48 ± 0,28 °C e entalpia de 78,31 ± 4,31 J.g-1 com pico endotérmico de fusão característico de uma forma cristalina que foi corroborado pela DRX, com habito cristalino do tipo agulha por MEV, apresenta baixa solubilidade aquosa e cinética de decomposição de ordem zero. O estudo de compatibilidade evidenciou possíveis incompatibilidades químicas e/ou físicas entre o LPSF/GQ-238 e os excipientes estudados. Concluí-se que a caracterização da NEQ obteve resultados sólidos sobre o comportamento físico e químicos de um protótipo antiparasitário para tratar a esquistossomose e a doença de chagas. / The 3-(2,6-difluoro-benzyl)-5-(5-bromo-1H-indol-3-ylmethylene)thiazolidine-2,4-dione (LPSF/GQ-238) is an indole-thiazolidine analogue with schistosomicidal and trypanocidal potential activity. Few reports in the literature show the effectiveness of a substance against schistosomiasis and Chagas disease simultaneously. These are considered debilitating diseases affecting millions of people worldwide. The objective of this study was to perform the physicochemical characterization of LPSF/QA-238 aiming to know their chemical and physical properties for the development of a new alternative treatment for the above diseases. The study covered the physicochemical characterization, thermal stability, and drug-excipient compatibility by spectroscopic techniques (IR, NMR), thermoanalytical (DSC, DSC-fotovisual, TG and Pyr-GC/MS), validation of analytical method, as also, XRD and SEM .The results of physicochemical evaluation of LPSF/QA-238 compared to different techniques allowed characterize it physical, chemical and morphologically. The prototype presented 99.5% purity, melting at 272.48 ± 0.28 °C and enthalpy of 78.31 ± 4.31 Jg1 , endothermic peak of melting characteristic of a crystalline form which was confirmed by XRD, with crystalline habit needle type observed in the SEM, has low aqueous solubility and kinetics of order decomposition zero.The compatibility study highlighted possible chemical and / or physical incompatibilities between LPSF / QA238 and the excipients studied.It is concluded that the new chemical entity characterization obtained actual results about the physical and chemical behavior of a prototype antiparasitic to treat schistosomiasis and Chagas disease.

Abstract The first part of this monograph discusses the asymmetric, ylide based, reagent controlled epoxidations. Both different chiral ylides and epoxidation processes, stoichiometric and catalytic, are reviewed. In the following part, new chiral sulfide catalysts were discovered as enantioselective catalysts for the Corey-Chaykovsky reaction (epoxidation of aldehydes via sulfonium ylides). Using a crystal structure of an oxazolidine derivative as a starting point, a thiazolidine ligand family was designed, synthesized and finally employed as catalysts in the asymmetric epoxidation of benzaldehyde. The ligands were prepared starting from L-valine, L-tert-leucine, D-penicillamine and L-cysteine. The differently tuned thiazolidine ligands were demonstrated to catalyze the formation of trans-stilbene oxide with varying enantioselectivities. On the basis of these results, a mechanistic rationale for the asymmetric induction was presented. The results heavily demonstrated the importance of ring rigidity as an affecting factor in the enantioselectivity of the tested thiazolidines.