Percorrer por autor "Gomes, Paula"
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- 11 - Collagen-like materials for tissue regeneration and repairPublication . Teixeira, Cátia; Ferraz, Ricardo; Prudêncio, Cristina; Gomes, PaulaPeptides can be designed to recreate the higher-order assembly (triple helix) and biological function of natural collagens. Collagen triple-helical domain contains Gly-Xaa-Yaa triplets where Xaa and Yaa are frequently proline and hydroxyproline, respectively. Glycine must be in every third position forming a hydrogen bond to an adjacent proline to stabilize collagen structure. Hydroxyproline residues are important in the thermal stability of the collagen triple-helix conformation. Although it is difficult to produce a stable triple helix, collagen-like peptides can be used to produce scaffolds that mimic natural tissue networks for biomedical engineering, without the liabilities of nonhuman natural collagens such us immunogenicity and pathogen transmission. This chapter describes the major approaches towards synthesis of collagen-like peptides, essentially aimed at production of artificial biocompatible and biofunctional frameworks for regenerative medicine.
- 4,9-Diaminoacridines and 4-Aminoacridines as Dual-Stage Antiplasmodial HitsPublication . Fonte, Mélanie; Tassi, Natália; Fontinha, Diana; Bóuzon-Arnáiz, Inês; Ferraz, Ricardo; Araújo, Maria J.; Fèrnandez-Busquets, Xavier; Prudêncio, Miguel; Gomes, Paula; Teixeira, CátiaMulti‐stage drugs have been prioritized in antimalarial drug discovery, as targeting more than one process in the Plasmodium life cycle is likely to increase efficiency, while decreasing the chances of emergence of resistance by the parasite. Herein, we disclose two novel acridine‐based families of compounds that combine the structural features of primaquine and chloroquine. Compounds prepared and studied thus far retained the in vitro activity displayed by the parent drugs against the erythrocytic stages of chloroquine‐sensitive and ‐resistant Plasmodium falciparum strains, and against the hepatic stages of Plasmodium berghei, hence acting as dual‐stage antiplasmodial hits.
- Anti-Pneumocystis carinii and antiplasmodial activities of primaquine-derived imidazolidin-4-onesPublication . Vale, Nuno; Collins, Margaret S.; Gut, Jiri; Ferraz, Ricardo; Rosenthal, Philip J.; Cushion, Melanie T.; Moreira, Rui; Gomes, PaulaA series of primaquine-derived imidazolidin-4-ones were screened for their in vitro activity against Pneumocystis carinii and Plasmodium falciparum W2 strain. Most compounds were active against P. carinii above 10 lg/mL and displayed slight to marked activity. The imidazolidin-4-ones most active against P. carinii were also those most active antiplasmodial agents, in the lM range. One of the tested imidazolidin-4-ones was slightly more active than the parent primaquine and may represent a lead com pound for the development of novel anti-P. carinii 8-aminoquinolines with increased stability and resistance to metabolic inactivation.
- Anti-pneumoscystis carinni activitiy of primaquine imidazolidin-4-onesPublication . Vale, Nuno; Ferraz, Ricardo; Azevedo, Joana; Araújo, Maria João; Moreira, Rui; Collins, Margaret S.; Cushion, Melanie T.; Gomes, PaulaPneumocystis pneumonia (PCP) is one of the most frequent causes of mortality among HIV-infected patients. Primaquine (PQ) is an antimalarial 8-aminoquinoline effective against PCP when given in combination with clindamycin. This has drawn the attention of Medicinal Chemists towards the anti-PCP activity of 8-aminoquinolines, not only confined to those exhibiting antimalarial activity [1]. It is thought that anti-PCP 8-aminoquinolines exert their anti-PCP activity by acting on the electronic transport and redox system of the P. carinii pathogen [1]. Recently, our research group has been developing imidazolidin-4-one derivatives of PQ (Scheme 1), targeting novel compounds with improved therapeutic action, namely, higher resistance to metabolic inactivation, lower toxicity and equal or higher antimalarial activity than that of the parent drug [2,3]. These imidazolidin-4-ones were seen to block the transmission of rodent malaria, caused by Plasmodium berghei on BalbC mice, to the mosquito vector Anopheles stephensi [3]. The anti-PCP activity of our PQ derivatives is now under study and preliminary in vitro assays [4] show that some of the compounds exhibit slight to moderate activity after a 72 h incubation period against P. carinii. In one case, the IC50 was comparable to that of parent PQ. Both these studies and forthcoming results from ongoing biological assays will be presented and discussed.
- Antifungal activity of Imidazolidin-4-ones of the antimalarial primaquinePublication . Ferraz, Ricardo; Fernandes, Rúben; Vieira, Mónica; Barros, Piedade; Gomes, Paula; Prudêncio, CristinaThe 5-Isopropyl-3-[4-(6-methoxy-quinolin-8-ylamino)-pentyl]-2,2-dimethyl-imidazolidin-4-one (ValPQacet) was sinthesized through acylation of the anti-malarial primaquine with α-valine and subsequent reaction of the resulting -aminoamide with propanone (Sheme 1).Imidazolidin-4-ones of the anti malarial primaquine are being sinthesized to develop new variants in order to improve more effective treatments against malaria . Recently it has been observed that primaquine derivates could have effect in a new kind of yeast . To study the fungicidal activity against Candida albicans, Candida tropicalis, Issatchenkia orientalis, Sacharomyces cerevisae, the ValPQacet was put in the form of the hydrochloride salt. The minimal inhibitory concentration (MIC) could be determined for all yeast in the concentration range assayed. Also was determined MIC’s of primaquine hydrochloride salt for all yeast, and this shows that the parent drug is less active than our compound. Further studies are being performed to determine viability and cellular injury with this drugs.
- Antimicrobial peptides as potential alternatives to prevent food spoilagePublication . Povkhanych, Maksym; Amorim, Maria Teresa; Ferraz, Ricardo; Prudêncio, Cristina; Gomes, Paula; Teixeira, CátiaIn 2015 it was estimated that on average the world consumption of antibiotics was 45 mg·kg−1 for cattle, 148 mg·kg−1 for chicken and 172 mg·kg−1 for pigs. Various studies suggested that low dosage exposure of antibiotics to livestock creates ideal conditions for the development of resistances and their spread between animals.1 Consequently, there is an increasingly robust global campaign to ban the use of synthetic antibiotics from agriculture, livestock management and the agro-food industry (AFI). Therefore, increasing the shelf life (commercial validity) of food products, and the use of sustainable production and consumption processes are some of the current challenges faced by the AFI. Furthermore, the current increase in consumer demand for natural 'organic' foods has forced companies and researchers to explore different ways to improve their market penetration by offering products with improvements in freshness, quality and food safety.2 This has made the AFI to suffer rapid changes in the last few years, including the use of antimicrobial peptides (AMP) as a mean of prevention of food spoilage.
- Antiproliferative organic salts derived from betulinic acid: Disclosure of an ionic liquid selective against lung and liver cancer cellsPublication . Silva, Ana Teresa; Cerqueira, Maria João; Prudêncio, Cristina; Fernandes, Maria Helena; Costa-Rodrigues, João; Teixeira, Cátia; Gomes, Paula; Ferraz, RicardoIn the last few years, we have been witnessing an increasing interest in ionic liquids (ILs) and organic salts, given their potential applications in biological and pharmaceutical sciences. We report the synthesis and in vitro evaluation of novel organic salts combining betulinate, known for its anticancer properties, with antimalarial drugs, primaquine, chloroquine, and mepacrine, and also with the trihexyltetradecylphosphonium ([P6,6,6,14]) cation. The salts were screened for their in vitro activity against tumor lines HepG2 (liver), MG63 (osteosarcoma), T47D (breast), A459 (lung), and RKO (colon), and also on normal human fibroblasts. All betulinates prepared displayed antiproliferative properties, with the trihexyltetradecylphosphonium betulinate standing out for its higher selectivity. This unprecedented disclosure of a betulinic acid (BA)-derived IL with selective antitumor activity constitutes a relevant first step toward development of novel anticancer therapies based on BA-derived IL.
- Bioactive peptides from milk proteins with antioxidant, anti-inflammatory, and antihypertensive activitiesPublication . Borges, Thaís; Coelho, Pedro; Prudêncio, Cristina; Gomes, Ana; Gomes, Paula; Ferraz, Ricardo; Coelho, Pedro; Prudêncio, Cristina; Ferraz, RicardoPeptides from protein ingredients exhibit key biological activities, including antimicrobial, antihypertensive, antioxidant, anti-inflammatory, analgesic, and immunomodulatory effects. Aligning with the One Health approach, there is growing investment in promoting pet health and well-being. As a result, sustainable functional ingredients are increasingly essential for pet food development. In this work, peptides derived from lactoferrins of different mammalian species were synthesized and their antioxidant, anti-inflammatory, and antihypertensive activities were investigated. This study examined the antioxidant, anti-inflammatory, antihypertensive activities, and cytotoxicity of bioactive peptides derived from lactoferrins of various mammalian species through spectroscopical methods. The peptides were produced via chemical synthesis (bottom-up approach). Peptides derived from bovine lactoferrin showed the most promising antioxidant and anti-inflammatory activities, whereas those derived from human lactoferrin showed the highest antihypertensive effects and the lowest cytotoxicity. In short, milk-derived peptides with antioxidant, anti-inflammatory, and antihypertensive activity were identified. This motivates further studies to better characterize these peptides, including their properties and pharmacokinetics in vivo, to assess their true potential as nutraceutical agents.
- Bioactivity of ionic liquidsPublication . Ferraz, Ricardo; Teixeira, Cátia; Gomes, Paula; Prudêncio, CristinaIonic liquids (ILs) were discovered a century ago, but it was only three decades ago that they started to catch the attention of the scientific commu- nity. ILs are defined as organic salts composed of an organic cation and an organic or inorganic anion2,3 that are stable below their melting point.
- Boosting cosmeceutical peptides: coupling imidazolium-based ionic liquids to pentapeptide-4 originates new leads with antimicrobial and collagenesis-inducing activitiesPublication . Gomes, Ana; Bessa, Lucinda J.; Fernandes, Iva; Aguiar, Luísa; Ferraz, Ricardo; Monteiro, Cláudia; Martins, M. Cristina L.; Mateus, Nuno; Gameiro, Paula; Teixeira, Cátia; Gomes, PaulaFollowing our previous reports on dual-action antibacterial and collagenesis-inducing hybrid peptide constructs based on “pentapeptide-4” (PP4, with amino acid sequence KTTKS), whose N-palmitoyl derivative is the well-known cosmeceutical ingredient Matrixyl, herein we disclose novel ionic liquid/PP4 conjugates (IL-KTTKS). These conjugates present potent activity against either antibiotic-susceptible strains or multidrug resistant clinical isolates of both Gram-positive and Gram-negative bacterial species belonging to the so-called “ESKAPE” group of pathogens. Noteworthy, their antibacterial activity is preserved in simulated wound fluid, which anticipates an effective action in the setting of a real wound bed. Moreover, their collagenesis-inducing effects in vitro are comparable to or stronger than those of Matrixyl. Altogether, IL-KTTKS exert a triple antibacterial, antifungal, and collagenesis-inducing action in vitro. These findings provide solid grounds for us to advance IL-KTTKS conjugates as promising leads for future development of topical treatments for complicated skin and soft tissue infections (cSSTI). Further studies are envisaged to incorporate IL-conjugates into suitable nanoformulations, to reduce toxicity and/or improve resistance to proteolytic degradation.