Publications by authors named "Celia Fernandez-Rubio"

Leishmaniasis remains one of the main public health problems worldwide, with special incidence in the poorest populations. Selenium and its derivatives can be potent therapeutic options against protozoan parasites. In this work, 17 aryl selenoates were synthesized and screened against three species of (, , and ).

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The search for new therapeutic targets and their implications in drug development remains an emerging scientific topic. BRCT-bearing proteins are found in Archaea, Bacteria, Eukarya, and viruses. They are traditionally involved in DNA repair, recombination, and cell cycle control.

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Article Synopsis
  • In 2020, the WHO launched a road map targeting the control and eradication of 20 neglected tropical diseases, focusing on conditions like leishmaniasis and Chagas disease.
  • The WHO has also been working on a Global Action Plan to combat Antimicrobial Resistance since 2015, highlighting the need for innovative treatment strategies in poor regions.
  • Natural peptide molecules (AMPs and CPPs) are emerging as promising alternatives to traditional therapies, as they show potential to enhance treatment effectiveness and reduce issues of toxicity and resistance in managing neglected zoonoses.
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  • Leishmaniasis, especially prevalent in countries like Italy and Spain, is spreading due to climate change and increased travel, necessitating the study of new parasite strains.
  • This research focused on two newly isolated parasite strains, NAV and TDL, from infected dogs, which showed slower growth and higher sensitivity to treatments compared to the established strain BCN 150.
  • The study found that NAV and TDL had enhanced infection capabilities and a different gene expression profile, suggesting they could be valuable for further research on leishmaniasis in Mediterranean regions.
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The lack of safe and cost-effective treatments against leishmaniasis highlights the urgent need to develop improved leishmanicidal agents. Antimicrobial peptides (AMPs) are an emerging category of therapeutics exerting a wide range of biological activities such as anti-bacterial, anti-fungal, anti-parasitic and anti-tumoral. In the present study, the approach of repurposing AMPs as antileishmanial drugs was applied.

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Around 15% of cancer cases are attributable to infectious agents. Epidemiological studies suggest that an association between leishmaniasis and cancer does exist. Recently, the homologue of PES1 in (LmjPES) was described to be involved in parasite infectivity.

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The current drug treatments against protozoan parasitic diseases including Chagas, malaria, leishmaniasis, and toxoplasmosis represent good examples of drug resistance mechanisms and have shown diverse side effects. Therefore, the identification of novel therapeutic strategies and drug compounds against such life-threatening diseases is urgent. According to the successful usage of selenium (Se) compounds-based therapy against some diseases, this therapeutic strategy has been recently further underlined against these parasitic diseases by targeting different parasite´s essential pathways.

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Leishmaniasis is a neglected tropical disease caused by spp. The improvement of existing treatments and the discovery of new drugs remain ones of the major goals in control and eradication of this disease. From the parasite genome, we have identified the homologue of the human oncogene in ().

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Since many of the currently available antileishmanial treatments exhibit toxicity, low effectiveness, and resistance, search and validation of new therapeutic targets allowing the development of innovative drugs have become a worldwide priority. This work presents a structure-based drug discovery strategy to validate the Lmj_04_BRCT domain as a novel therapeutic target in spp. The structure of this domain was explored using homology modeling, virtual screening, and molecular dynamics studies.

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  • Recent research highlights the connection between leishmaniasis and cancer in both humans and animals, particularly concerning the potential for misdiagnosis.
  • The study focuses on identifying and analyzing proteins that are commonly expressed in both Leishmania parasites and cancer cells to uncover potential therapeutic targets.
  • Findings suggest that these shared proteins play crucial roles in survival, development, and pathogenicity, which could lead to new treatment strategies for both diseases.
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Leishmaniasis includes a broad spectrum of pathological outcomes in humans caused by protozoan parasites from the genus Leishmania. In recent years, proteomic techniques have introduced novel proteins with critical functions in Leishmania parasites. Based on our report of a Chitin binding protein (CBP) in our previous immunoproteomic study, this article suggests that CBP might be an RNA binding protein (RBP) in Leishmania parasites.

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Miltefosine (MF), an alkylphospholipid originally developed for breast cancer treatment, is a highly active drug for the treatment against leishmaniasis, a neglected tropical disease considered the world's second leading cause of death by a parasitic agent after malaria. MF exhibits dose-limiting gastrointestinal side effects in patients and its penetration through lipophilic barriers is reduced. In this work we propose a reformulation of MF by incorporating the drug to poly(ethylene)oxide (PEO)-based polymeric micelles, specifically, D-α-tocopheryl polyethylene glycol succinate (TPGS) and Tetronic block copolymers (T904 and T1107).

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The identification and clarification of the mechanisms of action of drugs used against leishmaniasis may improve their administration regimens and prevent the development of resistant strains. Herein, for the first time, we describe the structure of the putatively essential Ser/Thr kinase LmjF.22.

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Toxoplasmosis is an important zoonotic disease transmitted to humans and warm-blooded animals by a ubiquitous parasite Toxoplasma gondii. One of the most common sources of human infection is the ingestion of tissue cysts through raw or undercooked meat. The present study was conducted to investigate a serological survey of Toxoplasma antibodies in cattle from Medea (North of Algeria).

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Conventional chemotherapy against leishmaniasis includes agents exhibiting considerable toxicity. In addition, reports of drug resistance are not uncommon. Thus, safe and effective therapies are urgently needed.

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Background: Cutaneous leishmaniasis (CL) skin lesions are the result of a deregulated immune response, which is unable to eliminate Leishmania parasites. The control of both, parasites and host immune response, is critical to prevent tissue destruction. The skin ulceration has been correlated with high TNF-α level.

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is the causative agent of leishmaniasis, a neglected tropical disease that affects more than 12 million people around the world. Current treatments are toxic and poorly effective due to the acquisition of resistance within populations. Thus, the pursuit for new antileishmanial drugs is a priority.

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The generation of new antileishmanial drugs has become a priority. Selenium and its derivatives stand out as having promising leishmanicidal activity. In fact, some parasites express selenoproteins and metabolize selenium.

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  • - The research achieved the first total synthesis of (Z)-16-methyl-11-heptadecenoic acid from the sponge Dragmaxia undata in seven steps, yielding 44%, using (trimethylsilyl)acetylene as a critical component.
  • - The synthesis method involved two key acetylide couplings that improved yields and allowed for the establishment of the compound's cis double bond stereochemistry through comprehensive spectral data.
  • - The synthesized fatty acid showed potential antiprotozoal activity against Leishmania donovani with an IC(50) of 165.5 μM and inhibited the enzyme LdTopIB, indicating promise for further pharmaceutical applications.
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The phylum Apicomplexa includes a large group of protozoan parasites responsible for a wide range of animal and human diseases. Destructive pathogens, such as Plasmodium falciparum and Plasmodium vivax, causative agents of human malaria, Cryptosporidium parvum, responsible of childhood diarrhoea, and Toxoplasma gondii, responsible for miscarriages and abortions in humans, are frequently associated with HIV immunosuppression in AIDS patients. The lack of effective vaccines, along with years of increasing pressure to eradicate outbreaks with the use of drugs, has favoured the formation of multi-drug resistant strains in endemic areas.

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The first total syntheses of the naturally occurring acetylenic fatty acids-6-heptadecynoic acid (59% overall yield) and 6-icosynoic acid (34% overall yield)-was accomplished in four steps. Using the same synthetic sequence the naturally occurring fatty acids (6Z)-heptadecenoic acid (46% overall yield) and (6Z)-icosenoic acid (27% overall yield) were also synthesized. The Delta(6) acetylenic fatty acids displayed good antiprotozoal activity towards Leishmania donovani promastigotes (EC(50) = 1-6 microg/mL), but the 6-icosynoic acid was the most effective in the series.

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Trypanosomatid (order Kinetoplastida)-borne neglected tropical diseases - African and American trypanosomiasis and leishmaniasis - are amongst the most devastating health threats of underdeveloped, developing and poor countries. Climatic changes due to global warming, tourism exchange and increasing migratory fluxes are re-distributing the endemic subtropical location of these diseases to a new scenario with a rising presence in developed countries during the last decades. In addition, the proved opportunistic transmission of these diseases through contaminated syringes shared by drug users, in combination with immunosuppression processes linked to HIV infections and the poor response to the typical treatments, point to AIDS patients as a sensitive sub-population prone to suffer from these diseases.

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