Identification of MAPK3 inhibitors against Leishmania spp. via in silico and in vitro approaches
Issued Date
2025-09-01
Resource Type
ISSN
1229845X
eISSN
1976555X
Scopus ID
2-s2.0-105017805558
Pubmed ID
40936270
Journal Title
Journal of Veterinary Science
Volume
26
Issue
5
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Veterinary Science Vol.26 No.5 (2025)
Suggested Citation
Kumsiri N., Siripattanapipong S., Aiebchun T., Nawattanapaibool N., Jongkon N., Choowongkomon K. Identification of MAPK3 inhibitors against Leishmania spp. via in silico and in vitro approaches. Journal of Veterinary Science Vol.26 No.5 (2025). doi:10.4142/jvs.25044 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/112517
Title
Identification of MAPK3 inhibitors against Leishmania spp. via in silico and in vitro approaches
Corresponding Author(s)
Other Contributor(s)
Abstract
Importance: Leishmaniasis, caused by Leishmania parasites, is a significant global health issue with limited treatment options. Mitogen-activated protein kinase 3 (MAPK3) plays a crucial role in parasite survival and immune evasion, making it a promising therapeutic target. Nevertheless, existing treatments have substantial side effects, and no specific MAPK3 inhibitors are available. Objective: This study evaluated the potential MAPK3 inhibitors capable of targeting L. donovani and L. martiniquensis using computational and experimental approaches. Methods: Five compounds from the NCI database were screened using an ADP-Glo Kinase Assay for MAPK3 inhibition. Half-maximal inhibitory concentration (IC<inf>50</inf>) analysis was performed to determine their potency. Molecular docking and molecular dynamics simulations were conducted to assess the binding interactions and stability. Cell-based assays were performed to evaluate the efficacy of these compounds against L. donovani and L. martiniquensis in the promastigote and amastigote stages. Results: NSC107522, NSC196515, and NSC84100 inhibited MAPK3, with IC<inf>50</inf> values of 2.69 µM, 4.96 µM, and 10.59 µM, respectively. NSC107522 showed the strongest binding affinity (ΔG<inf>bind</inf> = −111.20 kJ/mol) and reduced L. donovani survival in the promastigote (IC<inf>50</inf> = 2.68 µM) and amastigote (IC<inf>50</inf> = 4.04 µM) stages. NSC84100 exhibited superior activity against L. martiniquensis, with IC<inf>50</inf> values of 3.14 µM (promastigotes) and 2.61 µM (amastigotes). Conclusions and Relevance: NSC107522 and NSC84100 are promising MAPK3 inhibitors with species-specific activity. NSC107522 targets L. donovani, while NSC84100 is more effective against L. martiniquensis. These findings provide a foundation for developing targeted therapies against leishmaniasis, but further studies will be needed to determine their in vivo efficacy and optimize MAPK3-targeted drug design.