Percorrer por autor "Oliveira, Isabel"
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- Combining natural bile acids with old basic drugs affords new triple stage antimalarial surface-active ionic liquidsPublication . Silva, Ana Teresa; Oliveira, Isabel; Duarte, Denise; Moita, Diana; Prudêncio, Miguel; Nogueira, Fátima; Ferraz, Ricardo; Marques, Eduardo F.; Gomes, PaulaIonic liquids (ILs) are special organic salts that have been gaining momentum in medicinal chemistry. Despite their simple and cost-effective synthesis, ILs offer an easy access to structures of biological interest by combining bioactive molecules with opposite polarities, e.g., via simple ionic pairing of an acid with a base. This makes ILs of special interest for treating malaria. Since this disease is prevalent mainly in low-to-middle income countries, novel chemotherapeutic strategies must be kept affordable. Malaria is caused by Plasmodium parasites, whose complex life cycle includes three developmental stages in the host: the blood stage, the liver stage, and the gametocyte stage. This complexity turns the development of new effective drugs quite difficult, which is aggravated by the fast emergence of drug-resistant strains. This fact has often led to the disuse of several antimalarials, driving the need to find new ones with multiple-stage action. In this context, we have been working on new antimalarial ILs by mixing antimalarial aminoquinolines—chloroquine and primaquine—with natural lipids. Two new families of salts derived from those antimalarial drugs and naturally-occurring bile acids were now produced by acid-base neutralization, and evaluated for their antiplasmodial action. The chloroquine-derived bile salts were found active against all the three stages of parasite development in the host. Their behavior as surface-active ionic liquids (SAILs), i.e. their interfacial and self-aggregation properties, were also investigated, as they may contribute critically to their delivery and therapeutic action.
- Synthesis and physicochemical characterization of antimalarial surface-active ionic liquidsPublication . Silva, Ana Teresa; Oliveira, Isabel; Ferraz, Ricardo; Marques, Eduardo F.; Gomes, PaulaIonic liquids are a particular class of compounds that attract interest in medicinal chemistry due to the simplicity of their preparation. Novel structures with biological activity can be achieved through simple, cost-effective reactions.1 Reusing old ionizable drugs and improving their characteristics can be achieved economically and simply by mixing them with molecules of opposite charge. This approach is attractive for reviving old antimalarials, not only because of the prevalence of malaria in low- to middle-income countries, but also because several of these drugs are associated with malaria parasite resistance. In this context, our work has been focusing on synthesizing ionic liquids with potential antimalarial activity by mixing antimalarial aminoquinolines, specifically chloroquine, and primaquine, with natural lipids.2, 3 More recently, using an acid-base reaction between chloroquine and bile acids (Figure 1), we synthesized surface-active ionic liquids (SAILs), which proved to possess significant antiplasmodial activity in vitro. The presence of an amphiphilic anion in the ionic pair confers surfaceactive and self-aggregation properties to the ionic liquids. The interfacial and aggregations properties of these SAILs have been characterized by surface tension, electric conductivity, dynamic light scattering, and differential scanning microcalorimetry. Moreover, the interactions of SAILs with micelles of the block copolymer F127 have been studied with the aim of designing an efficient, robust, and biocompatible nanocarrier system for the encapsulation and in vivo release of these antimalarial ionic liquids.
- Synthesis od new surface-active ionic liquids derived from antimalarial drugs and bile acidsPublication . Silva, Ana Teresa; Oliveira, Isabel; Duarte, Denise; Moita, Diana; Prudêncio, Miguel; Nogueira, Fátima; Teixeira, Cátia; Ferraz, Ricardo; Marques, Eduardo F.; Gomes, PaulaMalaria is a parasitic disease that occurs mostly in low-income countries, thus its containment or, ultimately, eradication demands new methodologies and synthetic strategies that are simple and inexpensive. Ionic liquids (ILs) may assume a prominent role in this scenario, as they are catching the attention of the Medicinal Chemistry community owing to their intrinsic biological activity and affordable synthesis through straightforward methods. In this context, our focus consists of using an acid-base reaction between basic antimalarial aminoquinolines, such as chloroquine and primaquine, and natural amphiphilic acids, such as fatty and bile acids. The resulting ILs are expected to preserve the parent aminoquinolines' antimalarial action, while retaining the surface activity of the parent amphiphilic acids, thus facilitating the permeation of the whole IL structure through important biological barriers. In other words, our aim is to develop surface-active ionic liquids (SAILs) with intrinsic antimalarial properties. Results obtained thus far will be presented, demonstrating that SAILs can be produced which are active against different stages of malaria parasite development in the human host. Self-aggregation properties of these SAILs are currently under investigation and will be timely reported.