Submitted by Raphael Mota Garrido (raphaelmg91@hotmail.com) on 2018-04-24T15:12:00Z No. of bitstreams: 1 DissertaçãoVersãoFinalCorrigida.pdf: 638818 bytes, checksum: 25f1a3ef39a2378316e062d09b3a8057 (MD5) / Approved for entry into archive by Maria Luiza Carpi Semeghini (luiza@assis.unesp.br) on 2018-04-24T19:56:08Z (GMT) No. of bitstreams: 1 garrido_rm_me_assis_int.pdf: 638818 bytes, checksum: 25f1a3ef39a2378316e062d09b3a8057 (MD5) / Made available in DSpace on 2018-04-24T19:56:09Z (GMT). No. of bitstreams: 1 garrido_rm_me_assis_int.pdf: 638818 bytes, checksum: 25f1a3ef39a2378316e062d09b3a8057 (MD5) Previous issue date: 2018-03-06 / Atualmente, há esforços crescentes para o desenvolvimento de alternativas de manejo de plantas daninhas, devido ao aumento de espécies resistentes aos herbicidas e às preocupações ambientais. Mesmo que não se possa eliminar o uso de herbicidas convencionais, sua utilização pode ser reduzida pela descoberta de compostos bioativos, mais efetivos e/ou com menor toxicidade ao ambiente do que as moléculas que vem sendo usadas. O cinamaldeído e a curcumina são moléculas naturais que apresentam diversas atividades biológicas, e as chalconas são precursoras de flavonoides, que apresentam atividade alelopática, influenciando o desenvolvimento das plantas. Visando prospectar novos herbicidas, foi avaliado o potencial fitotóxico do cinamaldeído, da curcumina e de diferentes estruturas de chalconas metoxiladas. Inicialmente, foi feita triagem de 17 chalconas com bioensaio de desenvolvimento inicial com alface, para selecionar a mais promissora, e que seria testada com daninhas (seis espécies). Estas foram tratadas com 5 mL de solução 1 x 10-3 mol L-1 de cinamaldeído, curcumina ou 3,4-dimetoxichalcona (BC-18); como controle negativo e positivo usou-se água destilada e glifosato (componente ativo do Roundup®), respectivamente. Os comprimentos da raiz e parte aérea foram avaliados quando as plântulas dos controles negativos atingiram aproximadamente 5 cm. Todos os compostos induziram a inibição do crescimento quando comparados ao controle negativo, afetando a raiz e a parte aérea das plântulas. O cinamaldeído apresentou maior atividade fitotóxica que o glifosato em cinco espécies, já a curcumina apresentou maior inibição em uma espécie, e inibição igual ao glifosato em outras duas espécies. A BC-18 apresentou maior fitotoxicidade que o glifosato em três espécies e igual atividade em relação ao glifosato em outras duas. Conclui-se assim, que os três compostos possuem potencial herbicida, sendo o cinamaldeído o mais promissor, seguido pela BC-18. / Currently, there is increasing effort to develop weed management alternatives due to the increase of herbicide resistant species and environmental concerns. Even if the use of conventional herbicides cannot be eliminated, their use can be reduced by the discovery of bioactive compounds, more effective and/or with less toxicity to the environment than the molecules that are being used. Cinnamaldehyde and curcumin are natural molecules that exhibit various biological activities, and chalcones are precursors of flavonoids, which have allelopathic activity, influencing the development of plants. Aiming to prospect new herbicides, the phytotoxic potential of cinnamaldehyde, curcumin and different methoxylated chalcone structures was evaluated. Initially, 17 chalcones were screened in bioassay of initial development of lettuce, to select the most promising one, and tested with weeds (six species). These were treated with 5 mL of 1 x 10-3 mol L-1 solution of cinnamaldehyde, curcumin or 3,4-dimethoxychalcone (BC-18); as negative and positive control, distilled water and glyphosate (Roundup® active component) were used, respectively. The root and shoot lengths were evaluated when the seedlings of the negative controls reached approximately 5 cm. All the compounds induced growth inhibition when compared to the negative control, affecting the root and shoot of the seedlings. Cinnamaldehyde showed higher phytotoxic activity than glyphosate in five species, whereas curcumin showed greater inhibition in one species and glyphosate-like inhibition in two other species. BC-18 showed greater phytotoxicity than glyphosate in three species and glyphosate-like activity in other two species. It is concluded that the three compounds have herbicidal potential, with cinnamaldehyde being the most promising, followed by BC-18.

Polychlorinated biphenyls (PCBs) and their metabolic derivatives are ubiquitous environmental contaminants. These compounds are of concern because of their persistence and bioaccumulation in nature. PCBs and the hydroxylated metabolites have shown endocrine-disrupting activity. A method of detection in surface water samples is important to identify and quantify the environmental contamination. In this research we have attempted to develop a method of detection. Six representative polychloromethoxybiphenyls (PCMBs) were prepared. The corresponding polychlorobiphenylols, hydroxylated PCB metabolites (OH-PCBs), were prepared from the PCMBs. A method coupling solid phase extraction with liquid chromatography, on-line electrospray ionization, and mass spectrometry (SPE-LC/ESI/MS) was developed for detection of the OH-PCBs in distilled and surface water samples.

Yes / Itraconazole (ITR) is an antifungal drug with a limited bioavailability due to its poor aqueous solubility. In this study, ITR was used to investigate the impact of nanonisation and solid state change on drug’s apparent solubility and dissolution. A bottom up approach to the production of amorphous ITR nanoparticles (NPs), composed of 100% drug, with a particle diameter below 250 nm, using heat induced evaporative antisolvent nanoprecipitation (HIEAN) from acetone was developed. The NPs demonstrated improved solubility and dissolution in simulated gastrointestinal conditions when compared to amorphous ITR microparticles. NPs produced with polyethylene glycol (PEG) or its methoxylated derivative (MPEG) as a stabiliser enabled the production of smaller NPs with narrower particle size distribution and enhanced apparent solubility. MPEG stabilised NPs gave the greatest ITR supersaturation levels (up to 11.6 ± 0.5 μg/ml) in simulated gastric fluids. The stabilising polymer was in an amorphous state. Dynamic vapour sorption data indicated no solid state changes in NP samples with water vapour at 25 °C, while crystallisation was apparent at 50 °C. HIEAN proved to be an efficient method of production of amorphous ITR NPs, with or without addition of a polymeric stabiliser, with enhanced pharmaceutical properties. / Libyan Ministry of Higher Education and Scientific Research through the Libyan Embassy, London and supported by the Science Foundation Ireland under Grant No. 12/RC/2275 (Synthesis and Solid State Pharmaceuticals Centre).

<p>Over time, the Baltic Sea has been contaminated by increasing discharges of pollutants from human activities. Persistent organic pollutants (POPs) have caused toxic effects in wildlife and excess of nutrients have led to eutrophication. Furthermore, there are indications that certain polyhalogenated compounds similar in structure to man-made POPs are produced by the biota present in this sea. In the late 1990’s both methoxylated polybrominated diphenyl ethers (MeO-PBDEs) and hydroxylated-PBDEs (OH-PBDEs) were identified in fish and seals living in this environment. OH-PBDEs can originate from metabolism of PBDEs, but both OH- and MeO-PBDEs are also known to be natural products in marine environments. Another group of POPs, the polybrominated dibenzo-<i>p</i>-dioxins (PBDDs), are not produced commercially, but are known to be by-products of chemical industry and of the combustion of, e.g., brominated flame retardants (BFRs). In contrast to the OH- and MeO-PBDEs, PBDDs have not previously been shown to be natural products, although certain related compounds have been indicated to have a natural origin.</p><p>This thesis describes the identification of PBDDs, OH-PBDEs and MeO-PBDEs in algae, blue mussels and fish living in the Baltic Sea. Several of these compounds were also detected in cyanobacteria. Moreover, PBDDs were present in fish, mussels, shrimp and crabs from different regions of the Baltic Sea and from the west coast of Sweden, but not in organisms from freshwater environments. The levels of these compounds in Baltic fish generally exceeded those of their chlorinated analogues. The origin of the PBDDs identified is somewhat unclear, but the high levels present in blue mussels and the pattern of congeners observed indicate natural production. The presence of PBDDs, OH-PBDEs and MeO-PBDEs in fish and shellfish constitutes a potential risk to both humans and wildlife and requires further investigation.</p>

Over time, the Baltic Sea has been contaminated by increasing discharges of pollutants from human activities. Persistent organic pollutants (POPs) have caused toxic effects in wildlife and excess of nutrients have led to eutrophication. Furthermore, there are indications that certain polyhalogenated compounds similar in structure to man-made POPs are produced by the biota present in this sea. In the late 1990’s both methoxylated polybrominated diphenyl ethers (MeO-PBDEs) and hydroxylated-PBDEs (OH-PBDEs) were identified in fish and seals living in this environment. OH-PBDEs can originate from metabolism of PBDEs, but both OH- and MeO-PBDEs are also known to be natural products in marine environments. Another group of POPs, the polybrominated dibenzo-p-dioxins (PBDDs), are not produced commercially, but are known to be by-products of chemical industry and of the combustion of, e.g., brominated flame retardants (BFRs). In contrast to the OH- and MeO-PBDEs, PBDDs have not previously been shown to be natural products, although certain related compounds have been indicated to have a natural origin. This thesis describes the identification of PBDDs, OH-PBDEs and MeO-PBDEs in algae, blue mussels and fish living in the Baltic Sea. Several of these compounds were also detected in cyanobacteria. Moreover, PBDDs were present in fish, mussels, shrimp and crabs from different regions of the Baltic Sea and from the west coast of Sweden, but not in organisms from freshwater environments. The levels of these compounds in Baltic fish generally exceeded those of their chlorinated analogues. The origin of the PBDDs identified is somewhat unclear, but the high levels present in blue mussels and the pattern of congeners observed indicate natural production. The presence of PBDDs, OH-PBDEs and MeO-PBDEs in fish and shellfish constitutes a potential risk to both humans and wildlife and requires further investigation.