## Materials and Methods
### Statistical Analysis  
The in vitro biological assays were performed in triplicate and repeated three times independently. Data normality was assessed using the Shapiro-Wilk test, followed by a one-way ANOVA with Tukey's _post-hoc_ test for comparisons. Statistical analysis was conducted using GraphPad 8.0 software (GraphPad Software, Boston, MA, USA), with significance set at _p_\(<\) 0.05.  
**Supplementary Materials:** The following supporting information can be downloaded at: [[https://www.mdpi.com/article/10.3390/ph18060851/s1](https://www.mdpi.com/article/10.3390/ph18060851/s1)]([https://www.mdpi.com/article/10.3390/ph18060851/s1](https://www.mdpi.com/article/10.3390/ph18060851/s1)), Figure S1. Chromatographic profiles obtained through gas chromatography coupled with mass spectrometry (GC-MS); Figure S2. Effect of _C. longa_ extracts, curcumin, and quercetin (reference inhibitor) on _Li_ARG activity; Figure S3. Overlay of re-docked ABH (blue) and co-crystallized ABH (green) after re-docking approach in _Lm_ARG; Figure S4. Cytotoxic effect of _C. longa_ extracts, curcumin, and PAT (reference drug control) against different mammalian cells; Figure S5. Dose-response curves of _C. longa_ extracts, curcumin, and PAT (reference drug control) against _L. amazonensis_ and _L. infantum_ promastigotes; Figure S6. Effect of curcumin and PAT (reference drug control) on intracellular _L. infantum_ amastigotesode load.  
**Author Contributions:** Conceptualization, A.M.T.S., A.S.P. and I.A.R.; Formal analysis, F.F.S.S., M.A.M., J.R.A.S., W.S.M.F.N., A.C.F.A., R.A.C., E.M.B. and A.R.G.; Funding acquisition, A.C.F.A. and I.A.R.; Investigation, F.F.S.S., M.A.M., W.S.M.F.N., A.C.F.A., R.A.C., E.M.B. and A.R.G.; Resources, B.A.A.-V., C.R.R., A.M.T.S., D.N., A.S.P. and I.A.R.; Supervision, A.M.T.S., A.S.P. and I.A.R.; Writing--original draft, F.F.S.S., A.R.G., A.M.T.S. and I.A.R.; Writing--review and editing, J.R.A.S., A.C.F.A., B.A.A.-V., C.R.R. and D.N. All authors have read and agreed to the published version of the manuscript.  
**Funding:** This work was supported by grants from Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ, process number E-26/210.734/2023), Conselho Nacional Cientifico e Tecnologico (CNPq, process numbers 317271/2021-0; 315237/2023-6; 150963/2023-8; 447621/2024-6; 440011/2022-1), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), and Universidade Federal do Amazonas (UFAM).  
**Institutional Review Board Statement:** The animal study protocol was approved by the Institutional Ethics Committee of Universidade Federal do Rio de Janeiro (protocol code: 061/22-CEUA/UFRJ, date of approval: 23 June 2022).  
**Informed Consent Statement:** Not applicable.  
**Data Availability Statement:** The original contributions presented in this study are included in the article and Supplementary Material. Further inquiries can be directed to the corresponding authors.  
**Acknowledgments:** The authors thank the multi-user laboratory _Central Analtica_ of the School of Pharmacy at the Universidade Federal do Rio de Janeiro (UFRJ).  
**Conflicts of Interest:** The authors declare no conflicts of interest.