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Impact on the Sustainable Development Goals (SDGs)

Analysis of institutional authors

Esteve JAuthor

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March 30, 2023
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A Novel Family of Lysosomotropic Tetracyclic Compounds for Treating Leukemia

Publicated to:Cancers. 15 (6): 1912-1912 - 2023-03-01 15(6), DOI: 10.3390/cancers15061912

Authors: Carbo, Jose M; Cornet-Masana, Josep M M; Cuesta-Casanovas, Laia; Delgado-Martinez, Jennifer; Banus-Mulet, Antonia; Clement-Demange, Lise; Serra, Carme; Catena, Juanlo; Llebaria, Amadeu; Esteve, Jordi; Risueno, Ruth M M

Affiliations

- Author
Autonomous Univ Barcelona, Fac Biosci - Author
CSIC, Lab Med Chem & Synth, MCS, Inst Adv Chem Catalonia IQAC - Author
CSIC, SIMChem, Inst Adv Chem Catalonia IQAC - Author
Inst Invest Biomed August Pi & Sunyer IDIBAPS - Author
Josep Carreras Leukaemia Res Inst IJC - Author
Leukos Biotech - Author
Univ Barcelona, Fac Pharm - Author
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Abstract

Acute myeloid leukemia (AML) is a heterogeneous hematological cancer characterized by poor prognosis and frequent relapses. Aside from specific mutation-related changes, in AML, the overall function of lysosomes and mitochondria is drastically altered to fulfill the elevated biomass and bioenergetic demands. On the basis of previous results, in silico drug discovery screening was used to identify a new family of lysosome-/mitochondria-targeting compounds. These novel tetracyclic hits, with a cationic amphiphilic structure, specifically eradicate leukemic cells by inducing both mitochondrial damage and apoptosis, and simultaneous lysosomal membrane leakiness. Lysosomal leakiness does not only elicit canonical lysosome-dependent cell death, but also activates the terminal differentiation of AML cells through the Ca2+–TFEB–MYC signaling axis. In addition to being an effective monotherapy, its combination with the chemotherapeutic arsenic trioxide (ATO) used in other types of leukemia is highly synergistic in AML cells, widening the therapeutic window of the treatment. Moreover, the compounds are effective in a wide panel of cancer cell lines and possess adequate pharmacological properties rendering them promising drug candidates for the treatment of AML and other neoplasias. © 2023 by the authors.

Keywords

Acute myeloid leukemiaAnimal cellAnimal experimentAnimal modelAntineoplastic activityApoptosisArsenic trioxideArticleAutophagyBiomassBusulfanCancer cell lineCell deathCell viabilityCentrifugationChemical compoundClonogenesisComputer modelCytogeneticsCytotoxicityDrug discoveryEc50Flow cytometryGene expressionGood health and well-beingHek293 cell lineHumanHuman cellLeukemiaLeukemia cellLysosomeLysosome membraneLysosomotropic tetracyclic compoundMitochondrionMouseNew chemical entityNonhumanOncogene mycOxygen consumptionPolysorbate 80Signal transductionUbiquitinationUnclassified drugVolume of distributionWestern blotting

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Cancers due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2023, it was in position 78/322, thus managing to position itself as a Q1 (Primer Cuartil), in the category Oncology.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 1.72, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-08, the following number of citations:

  • WoS: 3
  • Scopus: 3
  • Europe PMC: 2
  • Open Alex: 3

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-08:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 5.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 10 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.
  • The number of mentions on the social network X (formerly Twitter): 2 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
Continuing with the social impact of the work, it is important to emphasize that, due to its content, it can be assigned to the area of interest of ODS 3 - Good Health And Well-being, with a probability of 80% according to the mBERT algorithm developed by Aurora University.