Lucía Román-Álamo

Barcelona Institute for Global Health

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Xavier Fernández‐Busquets

Institute for Bioengineering of Catalonia

YÁ

Yunuen Ávalos-Padilla

Barcelona Institute for Global Health

Elsa M. Arce

Universitat de Barcelona

Inés Bouzón‐Arnáiz

Barcelona Institute for Global Health

Diego Muñoz‐Torrero

Universitat de Barcelona

David Andreu

Barcelona Biomedical Research Park

Diana Moita

University of Lisbon

Arnau Biosca

Barcelona Institute for Global Health

Javier Valle

Barcelona Biomedical Research Park

Miguel Prudêncio

University of Lisbon

Cooperative Institutions

Universitat de Barcelona

Instituto de Salud Carlos III

Barcelona Institute for Global Health

Institute for Bioengineering of Catalonia

Centro de Investigación Biomédica en Red

Universitat Autònoma de Barcelona

University of Cagliari

Barcelona Institute for Science and Technology

Universitat de València

Centro Nacional de Microbiologia

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YAT2150 is irresistible in Plasmodium falciparum and active against Plasmodium vivax and Leishmania clinical isolates

Scientific Reports (2025)

Inés Bouzón‐Arnáiz Mukul Rawat Rachael Coyle Lionel Brice Feufack-Donfack Malen Ea

Plasmodium (life cycle)

10.1038/s41598-025-85346-y

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4-Deoxyphorbol inhibits HIV-1 infection in synergism with antiretroviral drugs and reactivates viral reservoirs through PKC/MEK activation synergizing with vorinostat

Biochemical Pharmacology (2020)

Humberto Erick de la Torre-Tarazona Rafael M. Mérida Jiménez Pilar Rubio Bueno S. Camarero Lucía Román-Álamo

10.1016/j.bcp.2020.113937

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Citations (14)

The protein aggregation inhibitor YAT2150 has potent antimalarial activity in Plasmodium falciparum in vitro cultures

BMC Biology (2022)

Inés Bouzón‐Arnáiz Yunuen Ávalos-Padilla Arnau Biosca Omar Caño-Prades Lucía Román-Álamo

Abstract Background By 2016, signs of emergence of Plasmodium falciparum resistance to artemisinin and partner drugs were detected in the Greater Mekong Subregion. Recently, the independent evolution of artemisinin resistance has also been reported in Africa and South America. This alarming scenario calls for the urgent development of new antimalarials with novel modes of action. We investigated the interference with protein aggregation, which is potentially toxic for the cell and occurs abundantly in all Plasmodium stages, as a hitherto unexplored drug target in the pathogen. Results Attempts to exacerbate the P. falciparum proteome’s propensity to aggregation by delivering endogenous aggregative peptides to in vitro cultures of this parasite did not significantly affect their growth. In contrast, protein aggregation inhibitors clearly reduced the pathogen’s viability. One such compound, the bis(styrylpyridinium) salt YAT2150, exhibited potent antiplasmodial activity with an in vitro IC 50 of 90 nM for chloroquine- and artemisinin-resistant lines, arresting asexual blood parasites at the trophozoite stage, as well as interfering with the development of both sexual and hepatic forms of Plasmodium . At its IC 50 , this compound is a powerful inhibitor of the aggregation of the model amyloid β peptide fragment 1-40, and it reduces the amount of aggregated proteins in P. falciparum cultures, suggesting that the underlying antimalarial mechanism consists in a generalized impairment of proteostasis in the pathogen. YAT2150 has an easy, rapid, and inexpensive synthesis, and because it fluoresces when it accumulates in its main localization in the Plasmodium cytosol, it is a theranostic agent. Conclusions Inhibiting protein aggregation in Plasmodium significantly reduces the parasite’s viability in vitro. Since YAT2150 belongs to a novel structural class of antiplasmodials with a mode of action that potentially targets multiple gene products, rapid evolution of resistance to this drug is unlikely to occur, making it a promising compound for the post-artemisinin era.

Proteostasis

Proteome

10.1186/s12915-022-01374-4

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The Transcription Machinery Driving Force: Why Did Nature Choose Phosphates?

Raúl Riera Aroche Esli C. Sánchez Moreno Yveth Marlene Ortiz-García ANDREA CAROLINA MACHADO SULBARAN L. Gary Leal

The dynamic phosphorylation of the human RNA Pol II CTD establishes a code applicable to all eukaryotic transcription processes. However, the ability of these specific post-translational modifications to convey molecular signals through structural changes remains unclear. We previously explained that each gene can be modeled as a combination of n circuits connected in parallel. RNA Pol II accesses these circuits and, through a series of pulses, matches the resonance frequency of the DNA qubits, enabling it to extract genetic information and quantum teleport it. Negatively charged phosphates react under RNA Pol II catalysis, increasing the electron density on the deoxyribose acceptor carbon. The first pulse of phosphorylation connects tyrosine to the nitrogenous base, while the subsequent pulses link the protein to molecular water through hydrogen bonds. The coupling of hydrogen proton transfer with electron transfer in water generates a supercurrent, which is explained by the correlation of pairs of the same type of fermions exchanging a boson. All these changes lead to the formation of a molecular protein-DNA-water condensate.

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10.20944/preprints202502.1028.v1

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Additional file 3 of The protein aggregation inhibitor YAT2150 has potent antimalarial activity in Plasmodium falciparum in vitro cultures

Figshare (2022)

Inés Bouzón‐Arnáiz Yunuen Ávalos-Padilla Arnau Biosca Omar Caño-Prades Lucía Román-Álamo

Additional file 3. Original, uncropped blots from Fig. 9.

10.6084/m9.figshare.21382526

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Non-Melanoma Skin Cancer: Dermatoscopic Diagnostic Clues in Dark-Skinned Mexican Individuals

Esli C. Sánchez Moreno Andrea Carolina Machado-Sulbarán Lizbeth Riera Leal Yveth Marlene Ortiz-García Lucía Román-Álamo

Background/Objectives: Skin cancer is increasingly prevalent. Non-melanoma skin cancers pose a challenge, as most lesions are diagnosed at later stages and often lead to complications. Although dermatoscopy has emerged as a valuable tool that enhances the confidence of dermatologists, specific patterns for accurately identifying various subtypes of non-melanoma skin cancer have yet to be detailed. This study aimed to investigate dermatoscopic clues that facilitate accurate diagnosis of non-melanoma skin cancer among dark-skinned Mexican individuals. There is insufficient acknowledgment of high skin cancer rates among non-Whites. Methods: The study included fifty-three patients diagnosed with non-melanoma skin cancer, aged 39 to 89, who visited an academic dermatology department for skin examinations. Two certified dermatologists evaluated at least three dermatoscopy images for each lesion. A biopsy was taken to confirm the preliminary diagnosis. Statistical analysis was performed using GraphPad Prism v8.0, considering a probability (p) value of less than 0.05 as significant. Results: Most patients were classified as phototype III. Patients with phototype IV were younger at the time of diagnosis. Basal cell carcinomas were the most common cancer subtype. Nodular and ulcerated tumors were the most prevalent morphology. The dermatoscopic examination revealed that 60% of the lesions were pigmented, with a predominance of polymorphic vascular patterns. Squamous cell carcinomas exhibited monomorphic vascular structures. Both groups' blood vessel arrangements and specific patterns were primarily radial. Conclusions: This study did not demonstrate the effectiveness of the non-melanoma skin cancer dermatoscopy criteria in distinguishing basal cell carcinomas from squamous cell carcinomas. However, certain factors, such as pigmentation and linear vessels, seem to occur more frequently in nodular basal cell carcinomas.

Dermatoscopy

Dark skin

10.20944/preprints202502.1232.v1

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In Vitro Evaluation of Aerosol Therapy with Pentamidine-Loaded Liposomes Coated with Chondroitin Sulfate or Heparin for the Treatment of Leishmaniasis

Pharmaceutics (2023)

Lucía Román-Álamo Mohamad Allaw Yunuen Ávalos-Padilla Maria Letizia Manca Maria Manconi

The second-line antileishmanial compound pentamidine is administered intramuscularly or, preferably, by intravenous infusion, with its use limited by severe adverse effects, including diabetes, severe hypoglycemia, myocarditis and renal toxicity. We sought to test the potential of phospholipid vesicles to improve the patient compliance and efficacy of this drug for the treatment of leishmaniasis by means of aerosol therapy. The targeting to macrophages of pentamidine-loaded liposomes coated with chondroitin sulfate or heparin increased about twofold (up to ca. 90%) relative to noncoated liposomes. The encapsulation of pentamidine in liposomes ameliorated its activity on the amastigote and promastigote forms of Leishmania infantum and Leishmania pifanoi, and it significantly reduced cytotoxicity on human umbilical endothelial cells, for which the concentration inhibiting 50% of cell viability was 144.2 ± 12.7 µM for pentamidine-containing heparin-coated liposomes vs. 59.3 ± 4.9 µM for free pentamidine. The deposition of liposome dispersions after nebulization was evaluated with the Next Generation Impactor, which mimics human airways. Approximately 53% of total initial pentamidine in solution reached the deeper stages of the impactor, with a median aerodynamic diameter of ~2.8 µm, supporting a partial deposition on the lung alveoli. Upon loading pentamidine in phospholipid vesicles, its deposition in the deeper stages significantly increased up to ~68%, and the median aerodynamic diameter decreased to a range between 1.4 and 1.8 µm, suggesting a better aptitude to reach the deeper lung airways in higher amounts. In all, nebulization of liposome-encapsulated pentamidine improved the bioavailability of this neglected drug by a patient-friendly delivery route amenable to self-administration, paving the way for the treatment of leishmaniasis and other infections where pentamidine is active.

Pentamidine

Atazanavir

10.3390/pharmaceutics15041163

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Curcumin or quercetin loaded nutriosomes as oral adjuvants for malaria infections

International Journal of Pharmaceutics (2023)

Federica Fulgheri Matteo Aroffu Miriam Ramírez Lucía Román-Álamo José Esteban Peris

Artemisinin, curcumin or quercetin, alone or in combination, were loaded in nutriosomes, special phospholipid vesicles enriched with Nutriose FM06®, a soluble dextrin with prebiotic activity, that makes these vesicles suitable for oral delivery. The resulting nutriosomes were sized between 93 and 146 nm, homogeneously dispersed, and had slightly negative zeta potential (around −8 mV). To improve their shelf life and storability over time, vesicle dispersions were freeze-dried and stored at 25 °C. Results confirmed that their main physico-chemical characteristics remained unchanged over a period of 12 months. Additionally, their size and polydispersity index did not undergo any significant variation after dilution with solutions at different pHs (1.2 and 7.0) and high ionic strength, mimicking the harsh conditions of the stomach and intestine. An in vitro study disclosed the delayed release of curcumin and quercetin from nutriosomes (∼53% at 48 h) while artemisinin was quickly released (∼100% at 48 h). Cytotoxicity assays using human colon adenocarcinoma cells (Caco-2) and human umbilical vein endothelial cells (HUVECs) proved the high biocompatibility of the prepared formulations. Finally, in vitro antimalarial activity tests, assessed against the 3D7 strain of Plasmodium falciparum, confirmed the effectiveness of nutriosomes in the delivery of curcumin and quercetin, which can be used as adjuvants in the antimalaria treatment. The efficacy of artemisinin was also confirmed but not improved. Overall results proved the possible use of these formulations as an accompanying treatment of malaria infections.

Zeta potential

10.1016/j.ijpharm.2023.123195

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Effect of the aggregated protein dye YAT2150 on Leishmania parasite viability

Antimicrobial Agents and Chemotherapy (2024)

Lucía Román-Álamo Yunuen Ávalos-Padilla Inés Bouzón‐Arnáiz Valentín Iglesias Jorge Fernández-Lajo

ABSTRACT The problems associated with the drugs currently used to treat leishmaniasis, including resistance, toxicity, and the high cost of some formulations, call for the urgent identification of new therapeutic agents with novel modes of action. The aggregated protein dye YAT2150 has been found to be a potent antileishmanial compound, with a half-maximal inhibitory concentration (IC 50 ) of approximately 0.5 µM against promastigote and amastigote stages of Leishmania infantum . The encapsulation in liposomes of YAT2150 significantly improved its in vitro IC 50 to 0.37 and 0.19 µM in promastigotes and amastigotes, respectively, and increased the half-maximal cytotoxic concentration in human umbilical vein endothelial cells to >50 µM. YAT2150 became strongly fluorescent when binding intracellular protein deposits in Leishmania cells. This fluorescence pattern aligns with the proposed mode of action of this drug in the malaria parasite Plasmodium falciparum , the inhibition of protein aggregation. In Leishmania major , YAT2150 rapidly reduced ATP levels, suggesting an alternative antileishmanial mechanism. To the best of our knowledge, this first-in-class compound is the only one described so far having significant activity against both Plasmodium and Leishmania , thus being a potential drug for the treatment of co-infections of both parasites.

Amastigote

IC50

10.1128/aac.01127-23

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Leveraging the Aggregated Protein Dye YAT2150 for Malaria Chemotherapy

Pharmaceutics (2024)

Claudia Camarero-Hoyos Inés Bouzón‐Arnáiz Yunuen Ávalos-Padilla Antonino N. Fallica Lucía Román-Álamo

: YAT2150 is a first-in-class antiplasmodial compound that has been recently proposed as a new interesting drug for malaria therapy.

10.3390/pharmaceutics16101290

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Citations (1)