Loading...
36 results
Search Results
Now showing 1 - 10 of 36
- Dual-action peptides as potential novel topical agents for treatment of skin and soft tissue infectionsPublication . Gomes, Ana; Bessa, Lucinda; Ferraz, Ricardo; Prudêncio, Cristina; Gameiro, Paula; Teixeira, Cátia; Gomes, PaulaChronic skin and soft-tissue infections (SSTI) such as diabetic foot ulcers (DFU) exhibit signs and symptoms that are consistent with localized bacterial biofilms that contribute to tissue destruction, delayed woundhealing and other serious complications. As such, most current approaches for advanced wound care aim at providing antimicrobial protection to the open wound together with a matrix scaffold (often collagenbased) to boost reestablishment of the skin tissue. While efficient production of recombinant human collagen remains an unmet goal, an alternative sensible option may be the design of formulations containing collagen-boosting instead of collagen-like components. Actually, collagen-boosting peptides, e.g., Matrikines®, are already used in cosmetics to promote extracellular matrix production, rebuilding structure and restoring all functions of healthy skin. Additionally, many antimicrobial peptides (AMP) can also act as wound-healing peptides, thus displaying the dual antimicrobial and tissue-regenerating properties highly desired in novel topical agents for treatment of SSTI. With the increasing prevalence of multi-drug resistant bacteria, and considering the burden that DFU alone represents to human health and healthcare facilities, the development of novel topical agents for effective treatment for this and other severe SSTI is an urgent need.
- Wound-Healing Peptides for Treatment of Chronic Diabetic Foot Ulcers and Other Infected Skin InjuriesPublication . Gomes, Ana; Teixeira, Cátia; Ferraz, Ricardo; Prudêncio, Cristina; Gomes, PaulaAs the incidence of diabetes continues to increase in the western world, the prevalence of chronic wounds related to this condition continues to be a major focus of wound care research. Additionally, over 50% of chronic wounds exhibit signs and symptoms that are consistent with localized bacterial biofilms underlying severe infections that contribute to tissue destruction, delayed wound-healing and other serious complications. Most current biomedical approaches for advanced wound care aim at providing antimicrobial protection to the open wound together with a matrix scaffold (often collagen-based) to boost reestablishment of the skin tissue. Therefore, the present review is focused on the efforts that have been made over the past years to find peptides possessing wound-healing properties, towards the development of new and effective wound care treatments for diabetic foot ulcers and other skin and soft tissue infections.
- Repurposing antiplasmodial leads for cancer: Exploring the antiproliferative effects of N-cinnamoyl-aminoacridinesPublication . Fonte, Mélanie; Rôla, Catarina; Santana, Sofia; Ferraz, Ricardo; Prudêncio, Miguel; Almeida, Joana; Ferraz, Ricardo; Prudêncio, Cristina; Teixeira, Cátia; Gomes, PaulaDrug repurposing and rescuing have been widely explored as cost-effective approaches to expand the portfolio of chemotherapeutic agents. Based on the reported antitumor properties of both trans-cinnamic acids and quinacrine, an antimalarial aminoacridine, we explored the antiproliferative properties of two series of N-cinnamoyl-aminoacridines recently identified as multi-stage antiplasmodial leads. The compounds were evaluated in vitro against three cancer cell lines (MKN-28, Huh-7, and HepG2), and human primary dermal fibroblasts. One of the series displayed highly selective antiproliferative activity in the micromolar range against the three cancer cell lines tested, without any toxicity to non-carcinogenic cells.
- New therapeutic approaches based on ionic liquidsPublication . Ferraz, Ricardo; Teixeira, Cátia; Prudêncio, Cristina; Teixeira, Dulce; Vieira, Mónica; Gomes, PaulaIonic liquids (ILs) are currently defined as salts (with at least one organic ion) stable above their melting point. They began to be used mainly as solvents, but quickly drew the attention of the Life Sciences, as some of the characteristics of those compounds may be relevant in therapeutic applications. ILs can show more interesting physicochemical properties at the level of active pharmaceutical ingredients such as water solubility, in addition to the fact that ILs (liquids at room temperature and/or human body temperature) do not present polymorphism, an aspect which often limits the conditions of use and therapeutic efficacy of solid active pharmaceutical ingredients. This line of research seeks, through a careful choice of the ions, to fine-tune some of these properties, and to study the combination of two bioactive molecules that have ionizable groups of opposite charge, forming ionic liquids with a dual therapeutic effect.
- Repurposing conventional antimycobacterial drugs using ionic liquidsPublication . Bento, Clara M.; Silva, Tânia; Aguiar, Luísa; Teixeira, Cátia; Gomes, Paula; Ferraz, Ricardo; Gomes, Maria SaloméNontuberculous mycobacteria, namely the species belonging to the Mycobacterium avium complex, are highly infectious opportunistic pathogens, which incidence is increasing worldwide. Treating these infections is challenging, due to long duration, high toxicity, and low effectiveness of available drugs. It is therefore urgent to find new therapeutic strategies, including the repurposing of old drugs. Ionic liquids (ILs) are organic salts made by the combination of two molecules with opposite polarities, which are gaining attention in drug development. Combining the right ions, it is possible to create ILs that could avoid polymorphism and solubility issues presented by solid conventional drugs, improving their absorption and desired dissolution rate. Besides increasing the bioavailability, the main goals when formulating a new IL is keeping or improving the bioactivity and cytotoxicity properties of the parental drug(s). The aim of our work is to evaluate the ability of ILs based on conventional antimycobacterial drugs, like clofazimine, aminosalicylic acid, and fluoroquinolones, to inhibit the viability and growth of M. avium in axenic culture and inside macrophages.
- Peptide conjugates for the topical treatment of infected woundsPublication . Gomes, Ana; Fernandes, Iva; Bessa, Lucinda; Ferreira, Mariana; Maciel, Joana; Plácido, Alexandra; Teixeira, Cátia; Leal, Ermelindo; Ferraz, Ricardo; Gameiro, Paula; Carvalho, Eugénia; Gomes, PaulaDue to widespread multidrug-resistant (MDR) microbes, efficient treatments for infected wounds are being exhausted.1 The symptoms of wound infection are consistent with local polymicrobial biofilms, which are difficult to eliminate and delay the healing process. The current standard of care requires oral antibiotics and other measures, often complex and distressing (e.g., amputations). A perfect treatment should promote both antimicrobial protection and fast tissue regeneration, to improve the inefficient healing in elderly people affected with, e.g., diabetes or venous/arterial insufficiency. 2 Considering the above, we advance peptide conjugates as potential active pharmaceutical ingredients for topical formulations to tackle skin infections. Such conjugates are anticipated to concomitantly display antimicrobial and anti-biofilm action along with fast healing through, e.g., collagenesis-inducing effects. Promising results were obtained with chimeric peptides combining a de novo designed antimicrobial peptide sequence 3 with a cosmetic peptide, used as anti-aging, with ability to induce collagen production.4 The best constructs exhibited: (i) antibacterial and anti-biofilm activity against Gram-positive and Gram-negative bacteria, including MDR clinical isolates; (iii) improved action against S. aureus (prevalent pathogen in chronically-infected wounds) in simulated wound fluid; and (v) antifungal activity. 5 The replacement of the antimicrobial peptide by an ionic liquid afforded a new conjugate, a peptide-ionic liquid construct, with broadspectrum antibacterial activity, antifungal action, and collagen-inducing effect. These results will be shown alongside the most recent findings that provide deeper insight into the mode of action of the best conjugates.
- Chloroquine Analogues as Leads against Pneumocystis Lung PathogensPublication . Gomes, Ana; Ferraz, Ricardo; Ficker, Lauren; Collins, Margaret S.; Prudêncio, Cristina; Cushion, Melanie T.; Teixeira, Cátia; Gomes, PaulaThe impact of Pneumocystis pneumonia (PcP) on morbidity and mortality remains substantial for immunocompromised individuals, including those afflicted by HIV infection, organ transplantation, cancer, autoimmune diseases, or subject to chemotherapy or corticosteroid-based therapies. Previous work from our group has shown that repurposing antimalarial compounds for PcP holds promise for treatment of this opportunistic infection. Following our previous discovery of chloroquine analogues with dual-stage antimalarial action both in vitro and in vivo, we now report the potent action of these compounds on Pneumocystis carinii in vitro Identification of chloroquine analogues as anti-PcP leads is an unprecedented finding.
- 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.
- The emerging role of ionic liquid-based approaches for enhanced skin permeation of bioactive molecules: a snapshot of the past couple of yearsPublication . Gomes, Ana; Aguiar, Luísa; Ferraz, Ricardo; Teixeira, Cátia; Gomes, PaulaTopical and transdermal delivery systems are of undeniable significance and ubiquity in healthcare, to facilitate the delivery of active pharmaceutical ingredients, respectively, onto or across the skin to enter systemic circulation. From ancient ointments and potions to modern micro/nanotechnological devices, a variety of approaches has been explored over the ages to improve the skin permeation of diverse medicines and cosmetics. Amongst the latest investigational dermal permeation enhancers, ionic liquids have been gaining momentum, and recent years have been prolific in this regard. As such, this review offers an outline of current methods for enhancing percutaneous permeation, highlighting selected reports where ionic liquid-based approaches have been investigated for this purpose. Future perspectives on use of ionic liquids for topical delivery of bioactive peptides are also presented.
- A new strategy against malaria – antimalarial ionic liquids derived from aminoquinolines and fatty acidsPublication . Silva, Ana Teresa; Teixeira, Cátia; Fontinha, Diana; Prudêncio, Cristina; Prudêncio, Miguel; Gomes, Paula; Ferraz, RicardoBased on the recent promising results obtained by us, where ionic liquids (ILs) derived from primaquine were found as triple-stage antimalarial hits, we have now produced, by simple, quantitative, and low-cost methods, new ILs via simple acid-base titration of antimalarial aminoquinolines (primaquine and chloroquine) with natural fatty acids (Figure 1). We have also synthesized, in good to high yields, the covalent amide analogues of these ILs (Figure 1), in order to establish how the nature of the chemical bond (ionic ammonium carboxylate versus covalent amide) between both building blocks influences the physico-chemical and biological properties of the final compounds. Results obtained thus far allow us to conclude that both ionic and covalent compounds (i) have higher thermostability than the parent drugs, and (ii) display remarkable in vitro activity against liver-stage malaria parasites.