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Background/Objectives: Leishmaniasis, a neglected disease caused by Leishmania spp. including L. amazonensis, urgently requires new treatments. Polyalthic acid (PA), a natural diterpene from Copaifera spp., has previously demonstrated significant antiparasitic potential. This study evaluated the leishmanicidal effects of polyalthic acid (PA), alone and with amphotericin B (AmpB), on L. amazonensis promastigote and amastigote forms. Results: PA showed significant activity against promastigotes, with 50% effective concentration (EC50) values of 2.01 μM at 24 h and an EC50 of 3.22 μM against amastigotes after 48 h. The PA and AmpB combination exhibited a synergistic effect on both forms without inducing cytotoxicity or hemolysis. Morphological changes in promastigotes, including vacuole formation and cell rounding, were more pronounced with the combination. Conclusions: These findings suggest that PA and AmpB together could form a promising new treatment strategy against Leishmania infections, offering enhanced efficacy without added toxicity. [ABSTRACT FROM AUTHOR]

We report the chemical composition of the crude leaf extracts obtained from Stizophyllum perforatum (Cham.) Miers (Bignoniaceae), a simple high-performance liquid chromatography–diode array detection (HPLC-DAD) method based on mangiferin as an internal standard to quantify verbascoside, and the verbascoside acute oral toxicity and antileishmanial activity. HPLC–high-resolution mass spectrometry–DAD (HPLC–HRMS–DAD) analyses of the crude ethanol S. perforatum leaf extracts (CE-1 and CE-2) revealed that verbascoside was the major constituent in both extracts. CE-1 was purified, and verbascoside and casticin, among other compounds, were isolated. The developed HPLC-DAD method was validated and met the required standards. Investigation of the CE-2 acute toxicity indicated a lethal dose (LD50) greater than 2,000 mg/kg of body weight. Both CE-1 and CE-2 exhibited antileishmanial activity. The isolated compounds, verbascoside and casticin, also displayed antileishmanial activity with effective concentrations (IC50) of 6.23 and 24.20 µM against promastigote forms and 3.71 and 18.97 µM against amastigote forms of Leishmania amazonensis, respectively, but they were not cytotoxic to J774A.1 macrophages. Scanning electron microscopy of the L. amazonensis promastigotes showed that the parasites became more rounded and that their plasma membrane was altered in the presence of verbascoside. Additionally, transmission electron microscopy demonstrated that vacuoles emerged, lipids accumulated, kinetoplast size increased, and interstitial extravasation occurred in L. amazonensis promastigotes exposed to verbascoside. These findings suggest that S. perforatum is a promising candidate for further in vivo investigations against L. amazonensis. [ABSTRACT FROM AUTHOR]

In this study, the chemical composition and in vitro antileishmanial activity of essential oils (EOs) from Protium heptaphyllum fresh young (PY-EO) and adult (PA-EO) leaves against promastigote forms of Leishmania amazonensis were evaluated. PY-EO and PA-EO leaves were highly active and activeagainst promastigote forms of L. amazonensis, since IC50 = 9.02 and 28.88 μg/mL, respectively. Chemical constituents of PY-EO and PA-EO leaves were identified by GC-MS and GC-FID. β-Caryophyllene (15.1%), α-amorphene (9.4%) and α-copaene (8.1%) were the major constituents identified in the PY-EO, whereas onlyβ-caryophyllene (15.0%), α-amorphene (9.1%) and α-copaene (8.0%) were identified at high concentrations in the PA-EO. Both PY-EO and PA-EO leaves showed moderate toxicity to Artemia salina by the Brine shrimp test.Results support the concept that several EOs, or at least some of their constituents, can become useful in the research of new therapeutic agents for leishmaniasis and in its clinical management. [ABSTRACT FROM AUTHOR]

• Determination of C-22 stereocenter configuration for two steroidal saponins through NMR techniques. • Quantification of eight steroidal saponins using an UHPLC-ESI-MS • High antileishmanial activity of steroidal saponins from S. paniculatum leaves, against of L. (L.) amazonensis. Solanum paniculatum L. is species whose fruits are widely consumed in Brazil as a tonic beverage with higher content of steroidal saponins. In this work, we developed an analytical method for the quantification of the eight saponins present in the 70 % ethanol extract from the leaves using ultra-high-performance liquid chromatography coupled to mass spectrometry (UHPLC-MS). Besides, the eight spirostanic saponins were screened for in vitro antileishmanial activity against promastigote and amastigote forms of Leishmania (L.) amazonensis. Substances 1 , 2 and 3 were found to be the most active compounds, with inhibitory concentration (IC 50) values of 8.51 ± 4.38, 10.75 ± 6.85 and 10.45 ± 4.21 μM, respectively, against promastigote forms and effective concentration (EC 50) values of >25, 17.73 ± 0.99 and 19.57 ± 0.84 μM, respectively, against amastigote forms. The cytotoxic test with compounds 1–3 evidenced low toxicity in murine macrophage cells, with values above 50 μM at concentration lower than 25 μM. These findings show that saponins 1–3 should be evaluated in further studies for the treatment of cutaneous leishmaniasis. [ABSTRACT FROM AUTHOR]