INTRODUÇÃO: As Doenças Tropicais Negligenciadas (DTNs) conceituam-se por serem doenças infecciosas ocasionadas por diversos tipos de parasitas, dentre eles as leishmanias sp., causadoras das leishmanioses, uma das diversas complicações relatadas em países com baixo subsídio em saúde, tornando-se necessário a revisão de novas moléculas. Dessa maneira, visando a utilização do método de biossíntese. OBJETIVO: Avaliar a possibilidade de utilização de nanopartículas de prata biológica (AgNPBs), obtidas de plantas no processo terapêutico contra as diferentes formas da Leishmania sp. , ampliando as perspectivas quanto aos produtos de avanço nanotecnológico para fins de tratamento. MÉTODOS: Desenvolveu-se uma revisão bibliográfica, utilizando das principais bases de dados, que trazem por incluso artigos, revisões de literatura, livros e revistas científicas, almejando a coleta de informações referentes ao tema previsto. RESULTADOS: Os resultados demonstraram que as plantas podem ser produtos de síntese de AgNPBs devido suas propriedades com valores baixos de CI50 (19,42 ± 2,76 µg/ml, 30,71 ± 1,91 µg/ml e 51,23 ± 2,20 µg/ml; 23,14 μg/ml, 0,0016μg/ml e 19,95 μg/ml em promastigota; 26,43 μg/ml, 0,0011μg/ml e 33,09 μg/ml para amastigotas) e bioativos como os flavonoides e alcaloides com alto poder antioxidante e anti-inflamatório, sendo suas vias mesmo não conclusivas mais efetivas que as convencionais. CONCLUSÃO: A biossíntese de nanopartículas de prata por plantas mostrou-se promissora como uma opção para carregar fármacos no tratamento das leishmanioses, devido à sua especificidade, biodisponibilidade e menores efeitos adversos. No entanto, há uma falta de estudos brasileiros aprofundados sobre o uso de extratos de plantas para formulação de nanopartículas. Portanto, é necessário coletar novas informações sobre a flora do país a fim de explorar as propriedades dos compostos de cada gênero e espécie, visando a nanotecnologia.

Background/Objectives: American trypanosomiasis, caused by Trypanosoma cruzi, remains a major public health challenge due to the limited efficacy and adverse effects associated with current treatments. Octyl gallate (OG), a semi-synthetic derivative of gallic acid, has demonstrated promising biological activities, including antiparasitic effects. Methods: The in vitro trypanocidal activity of OG was evaluated against T. cruzi. Mechanism of action studies included the inhibition of the trypanothione reductase enzyme and flow cytometry assays to measure cell death pathways (propidium iodide uptake). Additionally, the immunomodulatory potential of the compound was investigated by assessing cytokine production and innate immune responses. Results: In this study, the trypanocidal activity of OG against different evolutionary forms of T. cruzi was investigated. Using MTT-based viability assays, OG exhibited significant activity against epimastigotes (IC50 = 5.92 ± 0.47 µM), trypomastigotes (EC50 = 3.20 ± 0.14 µM), and intracellular amastigotes (EC50 = 4.07 ± 0.72 µM). The compound also demonstrated favorable selectivity indices, particularly against trypomastigotes and amastigotes, indicating selective toxicity toward the parasite compared to mammalian host cells. In infected macrophages, OG increased TNF-α and IL-12 production while reducing IL-10 and IL-6 levels, in addition to stimulating reactive oxygen species (ROS) and nitric oxide (NO) production, suggesting an immunomodulatory effect that contributes to parasite control. Molecular docking analyses revealed a favorable interaction between OG and trypanothione reductase (TR), while biochemical assays demonstrated reduced NADPH consumption, indicating interference with TR activity. Ultrastructural analysis revealed severe morphological alterations, including membrane disruption, cytoplasmic disorganization, mitochondrial swelling, and features consistent with apoptosis-like cell death. Conclusions: Collectively, these findings demonstrate that OG exhibits potent and selective trypanocidal activity associated with immunomodulatory effects, ultrastructural damage, and disruption of parasite redox metabolism through TR inhibition, supporting its potential as a candidate for future preclinical studies against Chagas disease.

Background/Objectives: Due to their toxicity and the limited efficacy of current therapies, Leishmaniases represent a major public health challenge. The search for new treatments is urgent. LQOF-G2 is a synthetic guanidine compound whose in vitro leishmanicidal potential has already been investigated by our group. The present study evaluates the in vivo efficacy, safety-related parameters, treatment-associated cytokine responses, and pharmacokinetic (PK) properties of the novel guanidine derivative LQOF-G2. Methods: Golden hamsters infected with Leishmania (Viannia) braziliensis were treated with LQOF-G2 (5 and 10 mg/kg, i.p.). Pharmacokinetic characterization was performed in BALB/c mice following intravenous and intraperitoneal administration. Results: Treatment with LQOF-G2 significantly reduced cutaneous lesion size and parasite burden at both the site of infection (up to 98.6 ± 0.8%) and in the lymph nodes (up to 99.7 ± 0.3%). No marked alterations were observed in the biochemical and hematological parameters evaluated at the tested doses. Treatment was associated with increased TNF-α and IFN-γ responses and reduced IL-10 levels following ex vivo antigen stimulation, consistent with a more pro-inflammatory/type-1-associated cytokine profile. Because murine cytokine ELISA reagents were used with golden hamster samples without independent species-specific analytical validation, these findings were considered exploratory and supportive rather than quantitatively validated evidence of an immunomodulatory mechanism. Pharmacokinetic characterization in BALB/c mice revealed moderate clearance (46 ± 4 mL/min/kg), a relatively large apparent volume of distribution (Vdss = 11 ± 1 L/kg), and a long elimination half-life (6.8 ± 0.4 h) following intravenous administration. After intraperitoneal administration, rapid absorption (Tmax = 0.25 h) and an absolute bioavailability of 44% were observed. Conclusions: Overall, these findings support LQOF-G2 as a candidate for further preclinical investigation in cutaneous leishmaniasis.