PubChem BioAssays 1063: A Poorly Exploited Source of New Antileishmanial Compounds

PubChem Bioassays (AID 1063) reported the in vitro testing of 196,141 compounds against Leishmania major promastigotes. Although these results have been publicly available since 2008, limited efforts on further testing of some of these compounds has been published. The aim of the present work was se...

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Main Authors: Sergio Sifontes-Rodríguez, Susana Meneses-Gómez, Alma Reyna Escalona-Montaño, Daniel Andrés Sánchez-Almaraz, Ofelia Pérez-Olvera, Aranza Regina Cañón Rosas, Pedro Zuriel Cruz Bautista, María Magdalena Aguirre-García
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Journal of Parasitology Research
Online Access:http://dx.doi.org/10.1155/japr/6338486
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author Sergio Sifontes-Rodríguez
Susana Meneses-Gómez
Alma Reyna Escalona-Montaño
Daniel Andrés Sánchez-Almaraz
Ofelia Pérez-Olvera
Aranza Regina Cañón Rosas
Pedro Zuriel Cruz Bautista
María Magdalena Aguirre-García
author_facet Sergio Sifontes-Rodríguez
Susana Meneses-Gómez
Alma Reyna Escalona-Montaño
Daniel Andrés Sánchez-Almaraz
Ofelia Pérez-Olvera
Aranza Regina Cañón Rosas
Pedro Zuriel Cruz Bautista
María Magdalena Aguirre-García
author_sort Sergio Sifontes-Rodríguez
collection DOAJ
description PubChem Bioassays (AID 1063) reported the in vitro testing of 196,141 compounds against Leishmania major promastigotes. Although these results have been publicly available since 2008, limited efforts on further testing of some of these compounds has been published. The aim of the present work was selecting a small set of compounds that were highly active in that primary assay and assessing their antileishmanial activity in vitro and in vivo. Selected compounds were 100% active in the primary assay at 10 μM, were not theoretically toxic, did not have structural features of pan assay interfering substances, had positive druglikeness, and were not cytotoxic, and their activity rate in previous assays reported in PubChem Bioassays was under 5%. Seven commercially available compounds were purchased and tested against L. major, Leishmania mexicana, Leishmania amazonensis, and Leishmania infantum promastigotes; in mouse peritoneal macrophages (cytotoxicity); and against L. mexicana intracellular amastigotes. Eventually, four compounds with appropriate selectivity and high activity against L. mexicana amastigotes were tested by intralesional route (1%, 20 μL) in a mouse model of cutaneous leishmaniasis. Four compounds were active (IC50<10 μM) against the promastigote stage of the four Leishmania species tested. These four compounds were also active (IC50<10 μM) in vitro against intracellular amastigotes and in vivo in mice experimentally infected with L. mexicana. Results demonstrated the potential of these compounds as antileishmanials and the high, unexploited potential of AID 1063 as a source of new antileishmanial agents.
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spelling doaj-art-e296ef3659374ec982750690fd300e7f2025-08-20T03:30:19ZengWileyJournal of Parasitology Research2090-00312025-01-01202510.1155/japr/6338486PubChem BioAssays 1063: A Poorly Exploited Source of New Antileishmanial CompoundsSergio Sifontes-Rodríguez0Susana Meneses-Gómez1Alma Reyna Escalona-Montaño2Daniel Andrés Sánchez-Almaraz3Ofelia Pérez-Olvera4Aranza Regina Cañón Rosas5Pedro Zuriel Cruz Bautista6María Magdalena Aguirre-García7Faculty of MedicineFaculty of PharmacyFaculty of MedicineFaculty of MedicineFaculty of MedicineFaculty of MedicineFaculty of MedicineFaculty of MedicinePubChem Bioassays (AID 1063) reported the in vitro testing of 196,141 compounds against Leishmania major promastigotes. Although these results have been publicly available since 2008, limited efforts on further testing of some of these compounds has been published. The aim of the present work was selecting a small set of compounds that were highly active in that primary assay and assessing their antileishmanial activity in vitro and in vivo. Selected compounds were 100% active in the primary assay at 10 μM, were not theoretically toxic, did not have structural features of pan assay interfering substances, had positive druglikeness, and were not cytotoxic, and their activity rate in previous assays reported in PubChem Bioassays was under 5%. Seven commercially available compounds were purchased and tested against L. major, Leishmania mexicana, Leishmania amazonensis, and Leishmania infantum promastigotes; in mouse peritoneal macrophages (cytotoxicity); and against L. mexicana intracellular amastigotes. Eventually, four compounds with appropriate selectivity and high activity against L. mexicana amastigotes were tested by intralesional route (1%, 20 μL) in a mouse model of cutaneous leishmaniasis. Four compounds were active (IC50<10 μM) against the promastigote stage of the four Leishmania species tested. These four compounds were also active (IC50<10 μM) in vitro against intracellular amastigotes and in vivo in mice experimentally infected with L. mexicana. Results demonstrated the potential of these compounds as antileishmanials and the high, unexploited potential of AID 1063 as a source of new antileishmanial agents.http://dx.doi.org/10.1155/japr/6338486
spellingShingle Sergio Sifontes-Rodríguez
Susana Meneses-Gómez
Alma Reyna Escalona-Montaño
Daniel Andrés Sánchez-Almaraz
Ofelia Pérez-Olvera
Aranza Regina Cañón Rosas
Pedro Zuriel Cruz Bautista
María Magdalena Aguirre-García
PubChem BioAssays 1063: A Poorly Exploited Source of New Antileishmanial Compounds
Journal of Parasitology Research
title PubChem BioAssays 1063: A Poorly Exploited Source of New Antileishmanial Compounds
title_full PubChem BioAssays 1063: A Poorly Exploited Source of New Antileishmanial Compounds
title_fullStr PubChem BioAssays 1063: A Poorly Exploited Source of New Antileishmanial Compounds
title_full_unstemmed PubChem BioAssays 1063: A Poorly Exploited Source of New Antileishmanial Compounds
title_short PubChem BioAssays 1063: A Poorly Exploited Source of New Antileishmanial Compounds
title_sort pubchem bioassays 1063 a poorly exploited source of new antileishmanial compounds
url http://dx.doi.org/10.1155/japr/6338486
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