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Propolis is a natural product widely used in folk medicine. Among its various applications, its antiparasitic properties stand out. Due to its great biodiversity, Brazil is a major producer of several types of propolis. This study proposes to evaluate the leishmanicidal properties of the hydroalcoholic extract of propolis collected in the southern region of Brazil (Brown propolis – HEBP) and its main isolated compounds: abietic acid (1), 13-epi-cupressic acid (2), 13-epi-torulosol (3), dehydroabietic acid (4), cis-communic acid (5) and ent-agatic acid (6). In general, the diterpenes did not show activity against the promastigotes of Leishmania (Leishmania) amazonensis at the evaluated concentrations. However, the HEBP was very active with an inhibition concentration of 50% at 8.32 µg/mL. Moreover, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) assays showed morphological and structural alterations in promastigote forms of L. (L.) amazonensis when incubated with HEBP. [ABSTRACT FROM AUTHOR]

Grazing management through pasture rotation has been mentioned as a viable alternative for the control of Rhipicephalus microplus; however, there is limited information on rotational grazing at field level. The objectives of this research were (1) to evaluate the effect of rotational grazing with 30 and 45 days of pasture rest and continuous grazing (without rest) on R. microplus tick loads in Brahman heifers and its most common crosses with Holstein; (2) to know the parasite dynamics of R. microplus under the three grazing systems in the humid tropics of Mexico; and (3) to determine the effect of the treatments on the characteristics of the pastures (availability of forage biomass, plant height, and soil cover). The experiment was carried out for 1 year from April 2022 to March 2023, with three grazing treatments: Treatments 1 and 2 considered rotational grazing with 30 (RT30) and 45 days of rest (RT45), respectively, and Treatment 3 as continuous grazing (CT00). Thirty calves from 8 to 12 months of initial age were distributed in each treatment (n = 10). Every 14 days, the number of engorged and semiengorged female ticks in cattle was determined. Concomitantly, the region's temperature, relative humidity, and rainfall were recorded, as well as the agronomic characteristics of the pasture. Rotational grazing animals with 30 days of rest had the highest number of ticks, while grazing animals with 45 days of rest had the least. Tick load dynamics among groups did not correlate with climatic variables (p > 0.05). The height and grass cover presented significant changes due to grazing (p < 0.05), which could influence the tick cycle by the exposure of the soil, modifying the microclimatic conditions and consequently harming the survival and development of R. microplus in the evaluated systems. The negative effect of rotational grazing on the nonparasitic phase of R. microplus deserves further studies. [ABSTRACT FROM AUTHOR]

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]

Background. Bovine trypanosomosis produces significant economic losses due to anemia, loss of body condition, and emaciation. The disease is transmitted biologically by tsetse flies and mechanically by biting flies such as Tabanus and Stomoxys. Therefore, this research is aimed at estimating the prevalence of bovine trypanosomosis and the apparent density of its vectors in the Etang Special District. Methods. A cross‐sectional study was employed from November 2016 to April 2017 for the prevalence and entomological survey. Trypanosoma species were identified using buffy coat and Giemsa staining techniques. Besides, the entomological surveys were conducted using NGU, pyramidal, biconical, and monoconical traps. The vectors were identified to their genus level based on their morphological features like size, color, wing venation, and proboscis. Result. A total of 457 bovine blood samples were collected and tested, of these 16 (3.50%) animals were positive for trypanosomosis. Similarly, 13 T. vivax (81.25%) and 3 T. congolense (18.75%) were the trypanosome species detected. The prevalence in the young (2.56%) and adult (3.99%) age groups was not statistically significant (P > 0.05). However, there were significant (P < 0.05) differences in prevalence between body condition scores, where poor is 6.31%, medium is 1.30%, and good is 0%. Moreover, the difference in mean PCV values between the parasitemic (20.97) and aparasitemic (28.58) groups was statistically significant (P < 0.05). Glossina flies were not found, although 1756 Tabanus and 52 Stomoxys biting flies were gathered. Accordingly, the overall apparent density of Glossina flies was zero (0), with biting flies (20.54) recorded per trap per day. Moreover, the apparent density of Tabanus and 52 Stomoxys was 39.01 and 1.18, respectively. Conclusion. This study confirmed that trypanosomosis and abundant mechanical vectors continue to be problems in the study area, resulting in cattle productivity losses. As a result, strategic management and prevention methods for trypanosomosis and associated vectors should be prioritized. Further investigation of vector needs to be conducted to clear out tsetse presence. [ABSTRACT FROM AUTHOR]

Neglected tropical diseases are significant causes of death and temporary or permanent disability for millions living in developing countries. Unfortunately, there is no effective treatment for these diseases. Thus, this work aimed to conduct a chemical analysis using HPLC/UV and GC/MS to identify the major constituents of the hydroalcoholic extracts of Capsicum frutescens and Capsicum baccatum fruits, evaluating these extracts and their constituents' schistosomicidal, leishmanicidal and trypanocidal activities. The results obtained for the extracts of C. frutescens are better when compared to those obtained for C. baccatum, which can be related to the different concentrations of capsaicin (1) present in the extracts. The lysis of trypomastigote forms results for capsaicin (1) led to a significant value of IC50 = 6.23 µM. Thus, the results point to capsaicin (1) as a possible active constituent in these extracts. [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]

Propolis is a natural product of great economic and pharmacological importance. The flora surrounding the bee communities is a determining factor in the composition of propolis and therefore in its biological and medicinal properties. Brown propolis is one of the most important types of propolis in Brazil, produced in the southeastern region. The ethanolic extract of a brown propolis sample from Minas Gerais state was chemically characterized for the subsequent development of a RP‐HPLC method, validated according to the standards of regulatory agencies. The leishmanicidal activity of this extract was assessed. The brown propolis was characterized by the presence of chemical markers reported on green propolis such as ferulic acid, coumaric acid, caffeic acid, cinnamic acid, baccharin, artepillin and drupanin, indicating a probable origin on Baccharis dracunculifolia. The developed method agreed with the parameters established by the validation guidelines, then proved to be reliable for the analysis of this type of propolis. The brown propolis displayed significant activity against Leishmania amazonensis with IC50 values of 1.8 and 2.4 μg/ml against the promastigote and amastigote forms, respectively. The studied propolis exhibited promising evidence for use as a natural source 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]

Introduction: Propolis is widely used in folk medicine, and many factors can affect its chemical composition, including abiotic factors that can influence plants and bees. Therefore, analytical methods are powerful techniques in the quality control of such products. Objective: Develop and validate an analytical method for quantifying volatile compounds in Brazilian brown propolis, and evaluate its biological activities. Methods: A gas chromatography flame ionisation detector (GC‐FID) analytical method was validated, attending the parameters of international validation guidelines as ANVISA 2017 and ICH 2005, for quantification of compounds present in volatile oils from propolis. Evaluation of cytotoxic, antimicrobial, and leishmanicidal activities of the oil. Results: The compounds 1,8‐cineole, terpinen‐4‐ol, α‐copaene, β‐caryophyllene, γ‐muurolene, nerolidol, spathulenol, and γ‐palmitolactone were isolated from the volatile fraction of a Brazilian brown propolis and used in the method validation. All the validation parameters of the method were satisfactory. The volatile fraction displayed a significant leishmanicidal activity, with half maximal inhibition concentration (IC50) = 21.3 μg/mL against amastigote forms and IC50 = 25.1 μg/mL against promastigote forms of Leishmania amazonensis. The oil also displayed an antibacterial effect by inhibiting the growth of Streptococcus mutans and Staphylococcus aureus at 25 μg/mL and 50 μg/mL, respectively, but it was not cytotoxic against AGP‐01, He‐La and CHO‐K1cell lines, with IC50 > 100 μg/mL. Conclusion: The GC‐FID method can be a useful tool in the quality control of propolis material. The southeast brown propolis showed a high chemical complexity in its volatile fraction, which displayed leishmanicidal activity and bactericidal activity. A GC‐FID method was developed for studying the volatile oil composition of one Brazilian Brown Propolis type produced in Minas Gerais state. From the volatile oil, obtained by hydrodistillation of brown propolis, the compounds 1,8‐cineole, terpinen‐4‐ol, α‐copaene, β‐caryophyllene, γ‐muurolene, nerolidol, spathulenol, and γ‐palmitolactone were isolated and used in the analytical method validation attended all the parameters of international validation guidelines as ANVISA and ICH. The oil displayed a significant leishimanicidal activity and antibacterial effect but it did not shown cytotoxicity. [ABSTRACT FROM AUTHOR]

Organogels (ORGs) are semi-solid materials, in which an organic phase is immobilized by a three-dimensional network composed of self-organized system, forming the aqueous phase. In this context, lipid–Pluronics (PLs) ORGs form a two-phase system which can be effectively used as skin delivery systems, favoring their permeation across the skin. In this study, we presented the development of ORG skin drug-delivery systems for curcumin (CUR), a liposoluble phenolic pigment extracted from the turmeric rhizome. In special, we designed the formulation compositions in order to carry high amounts of CUR soluble in oleic acid (OA), as organic phase, entrapped into an aqueous phase composed of micellar PL-based hydrogels by associating two polymers with different hydrophilic–lipophilic balances, Pluronic F-127 (PL F-127), and Pluronic L-81 (PL L-81), to enhance the permeation across the skin. Results revealed that the incorporation of PL L-81 favored the CUR incorporation into micelle–micelle interface. CUR insertion into OA-PL F-127/L-81 reduced both G'/G" relationship (∼16 x) and viscosity values (η* ∼ 54 mPa.s, at 32.5°C), disturbing the ORG network structural organization. In vitro permeation assays through Strat-M® skin-model membranes showed that higher CUR-permeated amounts were obtained for OA-PL F-127/L-81 (4.83 µg.cm−2) compared to OA-PL F-127 (3.51 μg.cm−2) and OA (2.25 μg.cm−2) or hydrogels (∼1.2 μg.cm−2, p < 0.001). Additionally, ORG formulations presented low cytotoxic effects and evoked pronounced antileishmanial activity (IC50 < 1.25 µg.ml−1), suggesting their potential use as skin delivery systems against Leishmania amazonensis. Results from this study pointed out OA-PL-based ORGs as promising new formulations for possible CUR topical administration. [ABSTRACT FROM AUTHOR]

The essential oils of Piper marginatum Jacq and Piper callosum Ruiz & Pav were obtained by hydrodistillation and tested in vitro against the adult worms of Schistosoma mansoni species. The chemical constituents were evaluated by Gas chromatography / Mass spectrometry. The main constituents of the essential oil of the leaves of P. marginatum were 3,4- (methylenedioxy) propiophenone (10.41 %), bicyclogermacrene (10.16 %) and germacrene D (9.93 %). The extraction of the aerial parts (branches, leaves and inflorescences) from P. callosum provided two essential oils, one of them being transparent and of greater density than the water presenting safrole (29.32 %), α-pinene (19.23 %) and β-pinene (14.31 %) as major constituents and another yellow oil of smaller density than the water with 92 % safrole. The essential oils exhibited a dose-dependent effect on decreased motor activity and death of parasites. The essential oil of P. marginatum caused death of 100 % of the parasites in the concentration of 50 μg/mL, while the PC+ (denser than water) and PC- (less dense than water) samples obtained from P. callosum caused 100 % death in the concentration of 100 μg/mL. [ABSTRACT FROM AUTHOR]

Inducing apoptosis is an interesting therapeutic approach to develop drugs that act against helminthic parasites. Researchers have investigated how curcumin (CUR), a biologically active compound extracted from rhizomes of Curcuma longa, affects Schistosoma mansoni and several cancer cell lines. This study evaluates how CUR influences the induction of apoptosis and oxidative stress in couples of adult S. mansoni worms. CUR decreased the viability of adult worms and killed them. The tegument of the parasite suffered morphological changes, the mitochondria underwent alterations, and chromatin condensed. Different apoptotic parameters were determined in an attempt to understand how CUR affected adult S. mansoni worms. CUR induced DNA damage and fragmentation and increased the expression of SmCASP3/7 transcripts and the activity of Caspase 3 in female and male worms. However, CUR did not intensify the activity of Caspase 8 in female or male worms. Evaluation of the superoxide anion and different antioxidant enzymes helped to explore the mechanism of parasite death further. The level of superoxide anion and the activity of Superoxide Dismutase (SOD) increased, whereas the activity of Glutathione-S-Transferase (GST), Glutathione reductase (GR), and Glutathione peroxidase (GPX) decreased, which culminated in the oxidation of proteins in adult female and male worms incubated with CUR. In conclusion, CUR generated oxidative stress followed by apoptotic-like-events in both adult female and male S. mansoni worms, ultimately killing them. [ABSTRACT FROM AUTHOR]

The schistosomicidal and cytotoxic activities of norneolignans isolated fromStyrax pohliiare used to relieve fever. The norneolignans homoegonol [2] and homoegonol glucoside [4] provided the best results against S. mansoni adult worms. At 200 μM, compounds 2 and 4 killed 25% and 50% of the parasites in 120 h, while egonol [1], homoegonol gentiobioside [3], and egonol gentiobioside [5] reduced their motor activity to 12.5%, 12.5%, and 37.5% in 120 h, respectively. With respect to the cytotoxic activity, the IC50values were greater than 800 μM for 1, 5, and 3 and 192.5 and 253.1 μM for 2 and 4, respectively. [ABSTRACT FROM PUBLISHER]

Context: Schistosomiasis is a major health problem worldwide. Thus, the search for new schistosomicidal agents from natural sources can provide prototypes for drug discovery. Objective: The present study investigated the chemical composition of the EtOAc fractions of Styrax pohlii Pohl (Styracaceae) (EF-SP) aerial parts and S. camporum A. DC. leaves (EF-SC), as well as schistosomicidal activities against Schistosoma mansoni adult worms, which have not yet been studied. Materials and methods: The crude ethanol extracts of S. camporum leaves and S. pohlii aerial parts (EE-SC and EE-SP) were partitioned with n-hexane, EtOAc, and n-BuOH. The EtOAc fractions were purified by preparative HPLC. The crude extracts, EtOAc fractions and pure compounds were tested against S. mansoni adult worms in vitro. Results: The purification procedure resulted in the isolation of kaempferol-3- O-(2′′,4′′-di- O-( E)- p-coumaroyl)-β- d-glucopyranoside ( 1), kaempferol-3- O-(2′′,6′′-di- O-( E)- p-coumaroyl)-β- d-glucopyranoside ( 2), quercetin ( 3), and kaempferol ( 4). The bioassay results indicated that EE-SC, EF-SC, EF-SP, and compounds 2 and 4 are able to separate coupled S. mansoni adult worms. Additionally, EE-SC, EF-SP, and compound 4 killed the adult schistosomes in vitro at 100 µg/mL and 100 µM. Discussion and conclusion: This is the first time that the presence of compounds 1- 2 in S. pohlii and 3-4 in S. camporum has been reported. Additionally, biological results indicated that S. pohlii and S. camporum have great potential as a source of active compounds. [ABSTRACT FROM AUTHOR]

Miconia langsdorffii Cogn. ( Melastomataceae), Roupala montana Aubl. (Proteaceae), Struthanthus syringifolius ( Mart.) (Loranthaceae), and Schefflera vinosa (Cham. & Schltdl.) Frodin (Araliaceae) are plant species from the Brazilian Cerrado whose schistosomicidal potential has not yet been described. The crude extracts, fractions, the triterpenes betulin, oleanolic acid, ursolic acid and the flavonoids quercetin 3-O-β-d-rhamnoside, quercetin 3-O-β-d-glucoside, quercetin 3-O-β-d-glucopyranosyl-(1-2)- α-l-rhamnopyranoside and isorhamnetin 3-O-β-d-glucopyranosyl-(1-2)-α-l-rhamnopyranoside were evaluated in vitro against Schistosoma mansoni adult worms and the bioactive n-hexane fractions of the mentioned species were also analyzed by GC MS. Betulin was able to cause worm death percentage values of 25% after 120 h (at 100 μ M), and 25% and 50% after 24 and 120 h (at 200 μ M), respectively; besides the flavonoid quercetin 3-O-β-d-rhamnoside promoted 25% of death of the parasites at 100 μ M. Farther the flavonoids quercetin 3-O-β-d-glucoside and quercetin 3-O-β-d-rhamnoside at 100 μ Mexhibited significantly reduction in motor activity, 75% and 87.5%, respectively. Biological results indicated that crude extracts of R. montana, S. vinosa, and M. langsdorffii and some n-hexane and EtOAc fractions of this species were able to induce worm death to some extent. The results suggest that lupane-type triterpenes and flavonoid monoglycosides should be considered for further antiparasites studies. [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]

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 (LD 50 ) 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 (IC 50 ) 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 ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Alves, Ozelin, Magalhães, Candido, Gimenez, Silva, Cunha, Januário, Tavares, Magalhães and Pauletti.)

Parasitic diseases continue to be a major worldwide health problem, and there is an urgent need for development of therapeutic drugs. This paper describes synthesis of dehydrodiferulic acid dilactone 1 and dehydrodisinapic acid dilactone 2 furofuran lignans by oxidative coupling of ferulic and sinapic acids, respectively. Their schistosomicidal, trypanocidal, and leishmanicidal activities were evaluated in vitro against Schistosoma mansoni adult worms, trypomastigote and amastigotes forms of Trypanosoma cruzi, and promastigote forms of Leishmania amazonensis. Compound 1 did not display significant schistosomicidal activity, but it presented potent trypanocidal activity, since it induced death of trypomastigotes and amastigotes with IC50/24h of 9.3μM and 7.3μM, respectively. Compound 2 had slight trypanocidal and schistosomicidal activities. None of the compounds were active against L. amazonensis. These results demonstrated that furofuran lignans are potentially useful for anti-parasitic drugs development and should be further investigated., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The neurotransmitter transporters of the SLC6 family play critical roles in the regulation of neurotransmission and are the primary targets of therapeutic agents used to treat clinical disorders involving compromised neurotransmitter signaling. The dopamine and norepinephrine transporters have been implicated in clinical disorders such as attention deficit hyperactivity disorder (ADHD) and substance abuse. The GABA transporters (GATs) serve as a target for anxiolytic, antidepressant, and antiepileptic therapies. In this work, the interaction with neurotransmitter transporters was characterized for a derivative of the lignan (-)-cubebin (1), namely, (-)-hinokinin (2). Using in vitro pharmacological assays, 2 selectively inhibited the human dopamine and norepinephrine transporters, in a noncompetitive manner possibly mediated by binding to a novel site within the transporters, and displayed low affinity for the serotonin transporter. Compound 2 also specifically inhibited the GAT-1 GABA transporter subtype. Compound 2 is not a substrate of the carriers as it had no effect on the efflux of either of the neurotransmitters investigated. This compound is inactive toward glutamate and glycine transporters. These results suggest that 2 may serve as a tool to develop new therapeutic drugs for ADHD and anxiety that target the DAT, NET, and GAT-1 transporters.

No fully effective treatment has been developed since the discovery of Chagas' disease. Since drug-resistant Trypanosoma cruzi strains are occurring and the current therapy is effective in the acute phase but with various adverse side effects, more studies are needed to characterize the susceptibility of T. cruzi to new drugs. Pre-mRNA maturation in trypanosomatids occurs through a process called trans-splicing, which is unusual RNA processing reaction, and it implies the processing of polycistronic transcription units into individual mRNAs; a short transcript spliced leader (SL RNA) is trans-spliced to the acceptor pre-mRNA, giving origin to the mature mRNA. Cubebin derivatives seem to provide treatments with less collateral effects than benznidazole and showed similar or better trypanocidal activities than benznidazole. Therefore, the cubebin derivatives ((-)-6,6'-dinitrohinokinin (DNH) and (-)-hinokinin (HQ)) interference in the mRNA processing was evaluated using T. cruzi permeable cells (Y and BOL (Bolivia) strains) following by RNase protection reaction. These substances seem to intervene in any step of the RNA transcription, promoting alterations in the RNA synthesis, even though the RNA processing mechanism still occurs. Furthermore, HQ presented better activity against the parasites than DNH, meaning that BOL strain seems to be more resistant than Y.