Work

Identification of MAPK3 inhibitors against Leishmania spp. via in silico and in vitro approaches

Year: 2025

Type: article

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 50 ) 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 50 values of 2.69 µM, 4.96 µM, and 10.59 µM, respectively.NSC107522 showed the strongest binding affinity (ΔG bind = -111.20kJ/mol) and reduced L. donovani survival in the promastigote (IC 50 = 2.68 µM) and amastigote (IC 50 = 4.04 µM) stages.NSC84100 exhibited superior activity against L. martiniquensis, with IC 50 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.

Source: Journal of Veterinary Science

DOI: 10.4142/jvs.25044

Authors: Nutnaree Kumsiri, Suradej Siripattanapipong, Thitinan Aiebchun, Namfon Nawattanapaibool, Nathjanan Jongkon, Kiattawee Choowongkomon

Institutions: Kasetsart University, Mahidol University, King Mongkut's University of Technology North Bangkok

Language: English

Topic: Research on Leishmaniasis Studies

Subfield: Public Health, Environmental and Occupational Health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $300