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Analysis of institutional authors

Martinez-Peinado, NAuthorCortes-Serra, NAuthorFenollar-Collado, AAuthorRos-Lucas, AAuthorGascon, JAuthorPinazo, MjAuthorIzquierdo, LCorresponding AuthorAlonso-Padilla, JCorresponding Author

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August 3, 2021
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Novel Purine Chemotypes with Activity against Plasmodium falciparum and Trypanosoma cruzi

Publicated to: Pharmaceuticals. 14 (7): 638- - 2021-07-01 14(7), DOI: 10.3390/ph14070638

Authors:

Martinez-Peinado, N; Lorente-Macías, A; García-Salguero, A; Cortes-Serra, N; Fenollar-Collado, A; Ros-Lucas, A; Gascon, J; Pinazo, MJ; Molina, IJ; Unciti-Broceta, A; Díaz-Mochón, JJ; Villatoro, MJPDY; Izquierdo, L; Alonso-Padilla, J
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Affiliations

Hosp Clin Univ Barcelona, Barcelona Inst Global Hlth ISGlobal, Barcelona 08036, Spain - Author
Univ Edinburgh, Canc Res UK Edinburgh Ctr, Inst Genet & Canc, Crewe Rd South, Edinburgh EH4 2XR, Midlothian, Scotland - Author
Univ Granada, Ctr Biomed Res, Inst Biopathol & Regenerat Med, Avda Conocimiento S-N, Granada 18100, Spain - Author
Univ Granada, Fac Pharm, Dept Med & Organ Chem, Campus Cartuja S-N, Granada 18071, Spain - Author
Univ Granada, Fac Pharm, Excellence Res Unit Chem Appl Biomed & Environm, Campus Cartuja S-N, Granada 18071, Spain - Author
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Abstract

Malaria and Chagas disease, caused by Plasmodium spp. and Trypanosoma cruzi parasites, remain important global health problems. Available treatments for those diseases present several limitations, such as lack of efficacy, toxic side effects, and drug resistance. Thus, new drugs are urgently needed. The discovery of new drugs may be benefited by considering the significant biological differences between hosts and parasites. One of the most striking differences is found in the purine metabolism, because most of the parasites are incapable of de novo purine biosynthesis. Herein, we have analyzed the in vitro anti-P. falciparum and anti-T. cruzi activity of a collection of 81 purine derivatives and pyrimidine analogs. We firstly used a primary screening at three fixed concentrations (100, 10, and 1 mu M) and progressed those compounds that kept the growth of the parasites < 30% at 100 mu M to dose-response assays. Then, we performed two different cytotoxicity assays on Vero cells and human HepG2 cells. Finally, compounds specifically active against T. cruzi were tested against intracellular amastigote forms. Purines 33 (IC50 = 19.19 mu M) and 76 (IC50 = 18.27 mu M) were the most potent against P. falciparum. On the other hand, 6D (IC50 = 3.78 mu M) and 34 (IC50 = 4.24 mu M) were identified as hit purines against T. cruzi amastigotes. Moreover, an in silico docking study revealed that P. falciparum and T. cruzi hypoxanthine guanine phosphoribosyltransferase enzymes could be the potential targets of those compounds. Our study identified two novel, purine-based chemotypes that could be further optimized to generate potent and diversified anti-parasitic drugs against both parasites.
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Keywords

cytotoxicity assaysphenotypic assaysplasmodium falciparumpurine derivativespurine metabolismtrypanosoma cruziAnalogsArtemisinin resistanceChagas-diseaseCrystal-structureCytotoxicity assaysDerivativesInhibitorsParasitesPhenotypic assaysPhosphoribosyltransferasePlasmodium falciparumPurine derivativesPurine metabolismPyrimi-dine analogsPyrimidine analogsSalvage pathwaysTransition-stateTrypanosoma cruzi

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Pharmaceuticals 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, 2021, it was in position 69/279, thus managing to position itself as a Q1 (Primer Cuartil), in the category Pharmacology & Pharmacy.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2026-01-21:

  • WoS: 13
  • Scopus: 12
  • Europe PMC: 8
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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 2026-01-21:

  • 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: 30.
  • 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: 30 (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: 6.
  • The number of mentions on the social network X (formerly Twitter): 9 (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.
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Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Granada; United Kingdom.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (MARTINEZ PEINADO, NIEVES) and Last Author (ALONSO PADILLA, JULIO).

the authors responsible for correspondence tasks have been IZQUIERDO LAZARO, LUIS and ALONSO PADILLA, JULIO.

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Awards linked to the item

A.F.-C.'s work was supported through SAF2016-76080-R (Spanish Ministry of Economy (AEI/FEDER, UE)), and PID2019-110810RB-I00 (Spanish Ministry of Science and Innovation) grants to L.I. We wish to give thanks for the support of the Generalitat of Catalonia Universities and Research Department, Spain (AGAUR; 2017SGR00924), and the funding from the Carlos III Health Institute (ISCIII), RICET Network for Cooperative Research in Tropical Diseases (ISCIII; RD12/0018/0010), and FEDER. N.M.-P., N.C.-S. and J.G.'s work was supported by the ISCIII project PI18/01054. M.-J.P.'s research was supported by the Generalitat of Catalonia Department of Health (PERIS 2016-2010 SLT008/18/00132). A.L.-M. was supported by the Spanish Ministry of Education, Culture, and Sports (FPU grant ref. 14/00818). We acknowledge support from the Spanish Ministry of Science, Innovation, and Universities through the Centro de Excelencia Severo Ochoa 2019-2023 Program (CEX2018-000806-S), and support from the Generalitat of Catalonia through the CERCA Program.
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