Version 1
: Received: 5 August 2024 / Approved: 5 August 2024 / Online: 5 August 2024 (16:47:25 CEST)
How to cite:
Sifontes-Rodríguez, S.; Escalona-Montaño, A. R.; Mondragón-Flores, R.; Mollineda Diogo, N.; Monzote Fidalgo, L.; Mondragón-Castelán, M. E.; Alardín Gutiérrez, F.; López-Enzana, L. A.; Sánchez-Almaraz, D. A.; Pérez-Olvera, O.; Aguirre-García, M. M. Compared Antileishmanial Activity of Clomiphene and Tamoxifen. Preprints2024, 2024080309. https://doi.org/10.20944/preprints202408.0309.v1
Sifontes-Rodríguez, S.; Escalona-Montaño, A. R.; Mondragón-Flores, R.; Mollineda Diogo, N.; Monzote Fidalgo, L.; Mondragón-Castelán, M. E.; Alardín Gutiérrez, F.; López-Enzana, L. A.; Sánchez-Almaraz, D. A.; Pérez-Olvera, O.; Aguirre-García, M. M. Compared Antileishmanial Activity of Clomiphene and Tamoxifen. Preprints 2024, 2024080309. https://doi.org/10.20944/preprints202408.0309.v1
Sifontes-Rodríguez, S.; Escalona-Montaño, A. R.; Mondragón-Flores, R.; Mollineda Diogo, N.; Monzote Fidalgo, L.; Mondragón-Castelán, M. E.; Alardín Gutiérrez, F.; López-Enzana, L. A.; Sánchez-Almaraz, D. A.; Pérez-Olvera, O.; Aguirre-García, M. M. Compared Antileishmanial Activity of Clomiphene and Tamoxifen. Preprints2024, 2024080309. https://doi.org/10.20944/preprints202408.0309.v1
APA Style
Sifontes-Rodríguez, S., Escalona-Montaño, A. R., Mondragón-Flores, R., Mollineda Diogo, N., Monzote Fidalgo, L., Mondragón-Castelán, M. E., Alardín Gutiérrez, F., López-Enzana, L. A., Sánchez-Almaraz, D. A., Pérez-Olvera, O., & Aguirre-García, M. M. (2024). Compared Antileishmanial Activity of Clomiphene and Tamoxifen. Preprints. https://doi.org/10.20944/preprints202408.0309.v1
Chicago/Turabian Style
Sifontes-Rodríguez, S., Ofelia Pérez-Olvera and María Magdalena Aguirre-García. 2024 "Compared Antileishmanial Activity of Clomiphene and Tamoxifen" Preprints. https://doi.org/10.20944/preprints202408.0309.v1
Abstract
Drug repositioning is an efficient strategy to search for new treatment alternatives that is especially valuable for neglected parasitic diseases such as leishmaniasis. Tamoxifen and raloxifene are selective estrogen receptor modulators (SERM) that have shown antileishmanial activity. Clomiphene is a SERM structurally similar to tamoxifen whose antileishmanial potential is unknown. That is why the objective of the present work was to evaluate its antileishmanial activity in vitro and in vivo, in comparison with tamoxifen. The inhibitory effect against promastigotes of L. amazonensis, L. major and L. mexicana was evaluated for both compounds; as well as the cytotoxicity against mouse peritoneal macrophages, the growth inhibitory activity in intracellular amastigotes of L. mexicana, and the in vivo activity in mice experimentally infected with L. mexicana. Clomiphene was about twice as active as tamoxifen against both promastigotes and intracellular amastigotes, with IC50 values of 1.7-3.3 µM for clomiphene and 2.9-6.4 µM for tamoxifen against all three species promastigotes; and 2.8 ± 0.2 µM and 3.7 ± 0.3 µM, respectively, against L. mexicana amastigotes. Clomiphene structurally affected several parasite organelles in a concentration-dependent fashion, leading to the death of both promastigotes and intracellular amastigotes. Interestingly, the macrophage host cell did not appear damaged with any of the clomiphene concentrations tested. By oral administration at 20 mg/kg for 14 days, both compounds showed similar effects in terms of reducing the growth of the lesions, as well as the weight of the lesions and the parasite load at the end of the follow-up period. The results showed the potential of SERM as antileishmanial drugs and support further testing of clomiphene and other compounds of this pharmacological group.
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
