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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 (EC 50 ) values of 2.01 μM at 24 h and an EC 50 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.

We have synthesized twenty-three 1,4-dihydropyridine derivatives (1,4-DHPs) by using a microwave-assisted one-pot multicomponent Hantzsch reaction and evaluated their antibacterial activity against a representative panel of cariogenic bacteria and their in vitro antileishmanial activity against Leishmania (L.) amazonensis promastigotes and amastigotes. Thirteen compounds were moderately active against Streptococcus sanguinis, Streptococcus mitis, and Lactobacillus paracasei. Compound 22 (diethyl 4-(3-methoxy-4-hydroxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) displayed moderate antibacterial activity against S. mitis and S. sanguinis, with a Minimum Inhibitory Concentration (MIC) of 500 μg/mL); compounds 8 (ethyl 2,7,7-trimethyl-4-(3-chlorophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) and 10 (ethyl 2,7,7-trimethyl-4-(3-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) were moderately active against S. sanguinis (MIC=500 μg/mL) and very active against L. amazonensis promastigotes (IC 50 =43.08 and 34.29 μM, respectively). Among the eight 1,4-DHPs that were active (IC 50 <50 μM) against L. amazonensis promastigotes, compound 13 (ethyl 2,7,7-trimethyl-4-(3,4,5-trimethoxyphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) was the most active (IC 50 =24.62 μM) and had a Selectivity Index (SI) higher than 4 compared to GM07492 A cells. On the other hand, compounds 7 (ethyl 2,7,7-trimethyl-4-(3-fluorophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) and 9 (ethyl 2,7,7-trimethyl-4-(2-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) were the most active against L. amazonensis amastigotes (IC 50 =12.53 and 13.67 μM, respectively; SI>7.9 and >7.3, respectively) after 24 h of treatment. Our results indicated that asymmetric 1,4-DHPs derived from dimedone exhibit antileishmanial potential., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

This study reports on the chemical composition and antileishmanial and anticandidal activities of volatile oils (VOs) of Schinus molle dried leaves (SM), Cinnamomum cassia branch bark (CC) and their blends. Major constituents of SM were spathulenol (26.93 %), β-caryophyllene (19.90 %), and caryophyllene oxide (12.69 %), whereas (E)-cinnamaldehyde (60.11 %), cinnamyl acetate (20.90 %) and cis-2-methoxycinnamic acid (10.37 %) were predominant in CC. SM (IC 50 =21.45 μg/mL) and CC (IC 50 =23.27 μg/mL) displayed good activity against L. amazonensis promastigotes, besides having good or moderate activity against nine Candida strains, with Minimum Inhibitory Concentration (MIC) values ranging from 31.25 to 250 μg/mL. While the three SM and CC blends were not more active than the VOs tested individually, they exhibited remarkably high antileishmanial activity, with IC 50 values ranging between 3.12 and 7.04 μg/mL, which is very similar to the IC 50 of amphotericin B (positive control)., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

We have evaluated eight p-coumaric acid prenylated derivatives in vitro for their antileishmanial activity against Leishmania amazonensis promastigotes and their antischistosomal activity against Schistosoma mansoni adult worms. Compound 7 ((E)-3,4-diprenyl-4-isoprenyloxycinnamic alcohol) was the most active against L. amazonensis (IC 50 =45.92 μM) and S. mansoni (IC 50 =64.25 μM). Data indicated that the number of prenyl groups, the presence of hydroxyl at C9, and a single bond between C7 and C8 are important structural features for the antileishmanial activity of p-coumaric acid prenylated derivatives., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

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 IC 50 = 6.23 µM. Thus, the results point to capsaicin ( 1 ) as a possible active constituent in these extracts.

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.)

Schistosomiasis, caused by Schistosoma mansoni Sambon, 1907, is a severe and widely distributed parasitic disease, affecting about 200 million people worldwide. The disease is recognized by elevated mortality rates, especially among those living in areas of poor sanitation. Currently, the chemotherapeutic treatment is solely based on using the praziquantel drug. Therefore, there is a need for the discovery of new medicines for the treatment of this parasitosis. Thus, this work aimed to evaluate the schistosomicidal activity of ethanolic crude extracts from the branches, leaves, flowers, and fruits of Handroanthus impetiginosus (Mart ex DC.) Masttos and characterize its metabolic profile by UPLC-ESI-QTOF analysis. Evaluation of plant extract on S. mansoni was carried out in adult worms in vitro, in which the mortality rate was quantified, and the damages in the tegument of the worms were monitored. All extracts induced changes in the viability of adult males of S. mansoni, causing the death of the parasites, which was directly dependent of the concentration.

Communication between Deaf and hearing individuals remains a persistent challenge requiring attention to foster inclusivity. Despite notable efforts in the development of digital solutions for sign language recognition (SLR), several issues persist, such as cross-platform interoperability and strategies for tokenizing signs to enable continuous conversations and coherent sentence construction. To address such issues, this paper proposes a non-invasive Portuguese Sign Language ( Língua Gestual Portuguesa or LGP) interpretation system-as-a-service, leveraging skeletal posture sequence inference powered by long-short term memory (LSTM) architectures. To address the scarcity of examples during machine learning (ML) model training, dataset augmentation strategies are explored. Additionally, a buffer-based interaction technique is introduced to facilitate LGP terms tokenization. This technique provides real-time feedback to users, allowing them to gauge the time remaining to complete a sign, which aids in the construction of grammatically coherent sentences based on inferred terms/words. To support human-like conditioning rules for interpretation, a large language model (LLM) service is integrated. Experiments reveal that LSTM-based neural networks, trained with 50 LGP terms and subjected to data augmentation, achieved accuracy levels ranging from 80% to 95.6%. Users unanimously reported a high level of intuition when using the buffer-based interaction strategy for terms/words tokenization. Furthermore, tests with an LLM-specifically ChatGPT-demonstrated promising semantic correlation rates in generated sentences, comparable to expected sentences.

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 IC 50 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., (© 2023 John Wiley & Sons Ltd.)

Chagas disease is a neglected tropical disease that affects more than 8 million people. Although there are therapies against this disease, the search for new drugs is important because the current treatments show limited effectiveness and high toxicity. In this work, eighteen dihydrobenzofuran-type neolignans (DBNs) and two benzofuran-type neolignans (BNs) were synthesized and evaluated against amastigote forms of two Trypanosoma cruzi strains. The in vitro cytotoxicity and hemolytic activity of the most active compounds were also evaluated and their relationships with T. cruzi tubulin DBNs were investigated by an in silico approach. Four DBNs demonstrated activity against the T. cruzi Tulahuen lac-Z strain (IC 50 from 7.96 to 21.12 µM), and DBN 1 exhibited the highest activity against the amastigote forms of the T. cruzi Y strain (IC 50 3.26 μM). Compounds 1 - 4 showed CC 50 values higher than antitrypanosomal activities, except for DBN 3 . All DBNs with antitrypanosomal activity demonstrated CH 50 higher than 100 µM. The in silico results indicated that DBNs 1 , 2 , and 4 are capable of destabilizing the dynamics of the tubulin-microtubule from the vinca site. These compounds displayed promising in vitro activity against T. cruzi , especially compound 1 , and can be considered molecular prototypes for the development of new antiparasitic drugs.

This article aims to investigate volatile constituents and antiacetylcholinesterase, antileishmanial and antiproliferative activities of hexane extracts from Capsicum chinense fruit (unripe bode pepper 'HE-UB' and ripe little beak pepper 'HE-RB'). HE-UB and HE-RB were screened by the microplate assay method to determine their antiacetylcholinesterase activity. Both exhibited inhibitory potential, i. e., IC 50 = 41.5 and 20.3 µg/mL, respectively. HE-UB (IC 50 = 67.19 µg/mL) and HE-RB (IC 50 = 38.16 µg/mL) exhibited antileishmanial activity against promastigote forms of Leishmania (Leishmania) amazonensis . In addition, HE-UB and HE-RB demonstrated cytotoxic activity against different human tumor cell lines with IC 50 ranging from 325.40 to 425.0 µg/mL. Both GC-FID and GC-MS analyses revealed that the major component in both extracts was E -caryophyllene. In short, HE-RB was more satisfactory than HE-UB in all in vitro activities under evaluation. These findings may be used as initial data for further studies of Capsicum species.

Praziquantel (PZQ) is the only drug available for community-based control programs which aim to reduce the prevalence and morbidity associated with schistosomiasis. Here, we synthesized and evaluated the schistosomicidal, biochemical and cytotoxic activities of EF24, a synthetic curcumin analog, against different isolates of Schistosoma mansoni. EF24 elicited marked phenotypic alterations at 10 μM against schistosomula and 42-day-old adult worms of the Naval Medical Research Institute (NMRI) isolate. EF24 had 50% effective concentration (EC 50 ) values of <10 μM against the Luis Evangelista (LE), Sergipe (SE), Belo Horizonte (BH) and Belo Horizonte less sensitive to PZQ (BH < PZQ) isolates of adult S. mansoni; however, the respective sensitivities of these isolates differed. Changes in the parasite included, vacuolization of the tegument and focal lysis of the interstitial tissue and muscle layers. Against 28-day-old juvenile worms (LE isolate), EF24 was about three times more potent than PZQ. After 6 h at 12.5 μM, EF24 increased reactive oxygen species (ROS) and the activity of the antioxidant enzyme, glutathione-S-transferase (GST), by 32 and 19% in female and male adult worms, respectively. By contrast, after 6 h at 12.5 μM glutathione reductase (GR) activity decreased by 43 and 30%, and glutathione peroxidase (GPx) activity decreased by 67 and 44% in females and males, respectively. EF24 was less cytotoxic to mammalian host cells than to S. mansoni, with selectivity indexes (SIs) of 1.8-3.4 and 2.7-7.5 for juvenile and adult worms, respectively. Given the current evidence for the in vitro schistosomicidal effect of EF24, the structure-activity relationship of additional analogs to identify new candidates for schistosomiasis treatment is warranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Lignan dinitrohinokinin displays important biological activities, which led to the preparation of its poly-ε-caprolactone nanoparticles. Kinetics analysis revealed initially slow drug release followed by a prolonged, moderate release 6 h later due to DNHK diffusion through the polymeric matrix. Molecular dynamics simulations show that DNHK molecules that interact stronger with other DNHK molecules near the PCL/DNHK surface are more difficult to dissociate from the nanoparticle. The smaller diameter nanocapsules with negative surface charge conferred good colloidal stability. The formulations showed a size distribution with monodisperse systems formation. In vivo evaluation of schistosomicidal activity against Schistosoma mansoni showed that DNHK, when incorporated into nanoparticles, caused egg number reduction of 4.2% and 28.1% at 40 mg/kg and 94.2% and 84.4% at 400 mg/kg in the liver and the spleen, respectively. The PCL nanoparticles were stable in aqueous dispersion and could be optimized to be used as a promising lignan release agent.

Schistosomiasis mansoni is an infectious parasitic disease caused by worms of the genus Schistosoma, and praziquantel (PZQ) is the medication available for the treatment of schistosomiasis. However, the existence of resistant strains reinforces the need to develop new schistosomicidal drugs safely and effectively. Thus, the (±)-licarin A neolignan incorporated into poly-Ɛ-caprolactone (PCL) nanoparticles and not incorporated were evaluated for their in vivo schistosomicidal activity. The (±)-licarin A -loaded poly(ε-caprolactone) nanoparticles and the pure (±)-licarin A showed a reduction in the number of worm eggs present in spleens of mice infected with Schistosoma mansoni. In addition, the (±)-licarin A incorporated in the concentration of 20 mg/kg and 200 mg/kg reduced the number of worms, presenting percentages of 56.3% and 41.7%, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This study aimed to investigate the chemical composition as well as the antibacterial, antiparasitic, and cytotoxic potentialities of the Brazilian Chrysopogon zizanioides root essential oil (CZ-EO) In addition, CZ-EO cytotoxicity to LLCMK 2 adherent epithelial cells was assessed. The major compounds identified in CZ-EO were khusimol (30.0 ± 0.3%), β-eudesmol (10.8 ± 0.3%), α-muurolene (6.0 ± 0.1%), and patchouli alcohol (5.6 ± 0.2%). CZ-EO displayed optimal antibacterial activity against Prevotella nigrescens , Fusobacterium nucleatum , Prevotella melaninogenica , and Aggregatibacter actinomycetemcomitans , with Minimum Inhibitory Concentration (MIC) values between 22 and 62.5 µg/mL and Minimum Bactericidal Concentration (MBC) values between 22 and 400 µg/mL. CZ-EO was highly active against the L. amazonensis promastigote and amastigote forms (IC 50 = 7.20 and 16.21 µg/mL, respectively) and the T. cruzi trypomastigote form (IC 50 = 11.2 µg/mL). Moreover, CZ-EO showed moderate cytotoxicity to LLCMK 2 cells, with CC 50 = 565.4 µg/mL. These results revealed an interesting in vitro selectivity of CZ-EO toward the L. amazonensis promastigote and amastigote forms (Selectivity Index, SI = 78.5 and 34.8, respectively) and the T. cruzi trypomastigote form (SI = 50.5) compared to LLCMK 2 cells. These results showed the promising potential of CZ-EO for developing new antimicrobial, antileishmanial, and antitrypanosomal drugs.

Spiranthera odoratissima A. St.-Hil. (Rutaceae) has been popularly used against abdominal pain and rheumatism. This study aimed at extracting hexane from S. odoratissima (HE-SO) leaves to identify and quantify its volatile compounds by GC-MS and GC-FID and to evaluate its antifungal, antileishmanial and antibacterial activities in vitro . HE-SO exhibited antileishmanial activity against promastigote forms of Leishmania (Leishmania) amazonensis (IC 50 = 38.16 µg/mL) and was moderately active against Xylella fastidiosa (MIC = 100 µg/mL). HE-SO also showed remarkable antifungal potential against six strains of Candida species, i. e., C. albicans , C. glabrata , C. parapsilosis , C. krusei , C. tropicalis and C. orthopsilosis . The lowest MIC values were between 31.25 and 250 µg/mL. Spathulenol (20.2%), τ-cadinol (11.7%), α-cadinol (9.4%), caryophyllene oxide (9.2%) and isoaromadendrene epoxide (8.2%) were the major components identified in HE-SO. Therefore, results showed that HE-SO has promising antileishmanial and antifungal actions.

Characterized as an acute and chronic parasitic disease, schistosomiasis mansoni has as its central pathology the formation of hepatic granulomas in response to the parasite's eggs trapped in the host's liver. In recent years, research on propolis has grown; however, there is little anthelmintic work on this bee product. In the propolis scenario, Brazilian ones receive attention, with green and red propolis standing out. This study aims to evaluate in vivo the standardized extract of Brazilian green propolis (Pex) against Schistosoma mansoni. The in vivo antiparasitic activity of Pex was conducted in female BALB/c mice infected with S. mansoni and of the three groups treated with Pex (300 mg/kg); G2 (35th to 42nd dpi) reduced the total worm burden by 55.32%, followed by G3 (42nd to 49th dpi) and G4 (49th to 56th dpi), with about 46%. Furthermore, G2 significantly reduced the total egg load in the ileum (59.33%) and showed an increase in the dead eggs. Similarly, histological analysis of the livers showed a significant reduction in the number and diameter of the granulomas. Based on these results, there is an interesting schistosomicidal activity of Pex and its potential against the formation of hepatic granulomas, paving the way for more detailed studies of propolis in the animal model of schistosomiasis mansoni., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

As part of the search for anti-trypanosomal agents, this work presents the production of sixteen derivatives. All of them were obtained from two natural diterpenes, one with kaurane skeleton ( ent -kaurenoic acid) and other with a pimarane skeleton ( ent -pimaradienoic acid). Then, the eighteen compounds were assayed against epimastigote form of Trypanosoma cruzi , with the derivatives showing increase of activity in relation to their precursors. Moreover, the most active derivative presented an IC 50 <12.5 µM (estimated 0.8 µM), lower than Benznidazole (IC 50 = 9.8 µM), used as control. The esterification of acid diterpenes showed to be an interesting way in the search for anti-trypanosomal agents.

This review article covers literature on the antischistosomal activity of essential oils (EOs) between 2011 and 2021. Criteria for classifying results from in vitro schistosomicidal assays are proposed for the first time. Parameters to evaluate the in vitro antischistosomal potential of EOs other than their ability to cause the death of Schistosoma mansoni adult worms (e. g., couple separation, egg laying, and egg development inhibition) are also addressed and discussed., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Cruzain, the main cysteine protease of Trypanosoma cruzi , plays key roles in all stages of the parasite's life cycle, including nutrition acquisition, differentiation, evasion of the host immune system, and invasion of host cells. Thus, inhibition of this validated target may lead to the development of novel drugs for the treatment of Chagas disease. In this study, a multiparameter optimization (MPO) approach, molecular modeling, and structure-activity relationships (SARs) were employed for the identification of new benzimidazole derivatives as potent competitive inhibitors of cruzain with trypanocidal activity and suitable pharmacokinetics. Extensive pharmacokinetic studies enabled the identification of metabolically stable and permeable compounds with high selectivity indices. CYP3A4 was found to be involved in the main metabolic pathway, and the identification of metabolic soft spots provided insights into molecular optimization. Compound 28 , which showed a promising trade-off between pharmacodynamics and pharmacokinetics, caused no acute toxicity and reduced parasite burden both in vitro and in vivo ., 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 © 2022 Pauli, Rezende Jr., Slafer, Dessoy, de Souza, Ferreira, Adjanohun, Ferreira, Magalhães, Krogh, Michelan-Duarte, Del Pintor, da Silva, Cruz, Dias and Andricopulo.)

Despite the current treatments against Chagas Disease (CD), this vector-borne parasitic disease remains a serious public health concern. In this study, we have explored the in vitro and/or in vivo trypanocidal and cytotoxic activities of the essential oils (EOs) obtained from Dysphania ambrosioides (L.) Mosyakin & Clemants (Amaranthaceae) (DA-EO), Lippia alba (Mill.) N.E. Brown (Verbenaceae) (LA-EO), and Tetradenia riparia (Hochst.) Codd (Lamiaceae) (TR-EO) grown in Brazil Southeast. DA-EO was the most active against the trypomastigote and amastigote forms in vitro; the IC 50 values were 8.7 and 12.2 μg mL -1 , respectively. The EOs displayed moderate toxicity against LLCMK2 cells, but the DA-EO showed high selectivity index (SI) for trypomastigote (SI=33.2) and amastigote (SI=11.7) forms. Treatment with 20 mg/kg DA-EO, LA-EO, or TR-EO for 20 days by intraperitoneal administration reduced parasitemia by 6.36 %, 4.74 %, and 32.68 % on day 7 and by 12.04 %, 27.96 %, and 65.5 % on day 9. These results indicated that DA-EO, LA-EO, and TR-EO have promising trypanocidal potential in vitro, whereas TR-EO has also potential trypanocidal effects in vivo., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

Propolis is a bee product that has been used in medicine since ancient times. Although its anti-inflammatory, antioxidant, antimicrobial, antitumor, and immunomodulatory activities have been investigated, its anti-parasitic properties remain poorly explored, especially regarding helminths. This review surveys the results obtained with propolis around the world against human parasites. Regarding protozoa, studies carried out with the protozoa Trypanosoma spp. and Leishmania spp. have demonstrated promising results in vitro and in vivo. However, there are fewer studies for Plasmodium spp., the etiological agent of malaria and less so for helminths, particularly for Fasciola spp. and Schistosoma spp. Despite the favorable in vitro results with propolis, helminth assays need to be further investigated. However, propolis has shown itself to be an excellent natural product for parasitology, thus opening new paths and approaches in its activity against protozoa and helminths., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

Numerous studies have investigated the chemical composition and biological activities of essential oils from different Citrus species fruit peel, leaves and flowers. This paper aims to investigate the chemical composition, larvicidal and antileishmanial activities of essential oil from Citrus reticulata fruit peel (CR-EO). CR-EO was obtained by hydrodistillation in a Clevenger-type apparatus and its chemical composition was analyzed by GC-MS and GC-FID. Limonene (85.7%), ɣ-terpinene (6.7%) and myrcene (2.1%) were identified as its major components. CR-EO showed high activity against promastigote forms of Leishmania amazonensis (IC50 = 8.23 µg/mL). CR-EO also exhibited high larvicidal activity against third instar Aedes aegypti larvae at a lethal concentration (LC50 = 58.35 µg/mL) and 100% mortality at 150 µg/mL. This study suggests, for the first time, the potential use of CR-EO against this important mosquito-borne viral disease caused by the genus Aedes.

Chagas disease is a tropical disease caused by the protozoan parasite Trypanosoma cruzi and currently affects millions of people worldwide. Curcumin (CUR), the major constituent of turmeric spice (dry powder of Curcuma longa L. plant rhizomes and roots), exhibits antiparasitic activity against protozoan parasites in vitro . However, because of its chemical instability, poor cellular uptake and limited bioavailability it is not suitable for clinical use. The objective of this study was to synthesize and evaluate in vitro CUR monoketone analog dibenzalacetone (DBA 1 ) and its non-phenolic, methoxy ( 2-4 ) and chloro ( 5 ) derivatives for better stability and bioavailability against T. cruzi . Diveratralacetone, the tetramethoxy DBA (DBA 3 ), was found to be the CUR analog with most enhanced activity against the amastigote forms of four strains of T. cruzi tested (Brazil, CA-I/72, Sylvio X10/4 and Sylvio X10/7) with 50% inhibitory concentration (IC 50 ) < 10 μM (1.51-9.63 μM) and selectivity index (SI) > 10 (C2C12 non-infected mammalian cells). This was supplemented by time-course assessment of its anti- T. cruzi activity. DBA 1 and its dimethoxy (DBA 2 ) and hexamethoxy (DBA 4 ) derivatives were substantially less active. The inactivity of dichloro-DBA (DBA 5 ) was indicative of the important role played by oxygenated groups such as methoxy in the terminal aromatic rings in the DBA molecule, particularly at para position to form reactive oxygen species essential for anti- T. cruzi activity. Although the DBAs and CUR were toxic to infected mammalian cells in vitro , in a mouse model, both DBA 3 and CUR did not exhibit acute toxicity or mortality. These results justify further optimization and in vivo anti- T. cruzi activity evaluation of the inexpensive diveratralacetone for its potential use in treating Chagas disease, a neglected parasitic disease in economically challenged tropical countries., (© 2021 The Author(s).)

Fractionation of extracts from the culture broth of the marine-derived fungus, Paecilomyces sp. 7A22, resulted in the isolation of the harzialactone A ( HA ), a known compound previously isolated from fungi of marine environments. The chemical structure of HA was determined by spectroscopic analyses. Upon evaluation of HA on antileishmanial assays against Leishmania amazonensis , HA exhibited significant activity against promastigotes forms with IC 50 of 5.25 µg mL -1 and moderate activity against intracellular amastigotes with IC 50 of 18.18 µg mL -1 . This is the first report on the antileishmanial activity of HA , and the effects of HA presented in this work suggest that this class of compounds are suitable for future biological in vitro and in vivo studies for the search of natural products with activity against Leishmania spp. Furthermore, the present results corroborate marine-derived fungi as a promising source of natural products with antiparasitic activity.

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 (IC 50 ) = 21.3 μg/mL against amastigote forms and IC 50 = 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 IC 50 > 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., (© 2020 John Wiley & Sons, Ltd.)

Deubiquitinating enzymes (DUBs) are conserved in Schistosoma mansoni and may be linked to the 26S proteasome. Previous results from our group showed that b-AP15, an inhibitor of the 26S proteasome DUBs UCHL5 and USP14 induced structural and gene expression changes in mature S. mansoni pairs. This work suggests the use of the nonselective DUB inhibitor PR-619 to verify whether these enzymes are potential target proteins for new drug development. Our approach is based on previous studies with DUB inhibitors in mammalian cells that have shown that these enzymes are associated with apoptosis, autophagy and the transforming growth factor beta (TGF-β) signaling pathway. PR-619 inhibited oviposition in parasite pairs in vitro, leading to mitochondrial changes, autophagic body formation, and changes in expression of SmSmad2 and SmUSP9x, which are genes linked to the TGF-β pathway that are responsible for parasite oviposition and SmUCHL5 and SmRpn11 DUB maintenance. Taken together, these results indicate that DUBs may be used as targets for the development of new drugs against schistosomiasis., (Copyright © 2021. Published by Elsevier B.V.)

The efficacy of Licochalcone A (LicoA) and its two analogs were reported against Leishmania (Leishmania) amazonensis and Leishmania (Leishmania) infantum in vitro , and in experimental model of L. (L.) infantum in vitro . Initially, LicoA and its analogs were screened against promastigote forms of L. (L.) amazonensis . LicoA was the most active compound, with IC 50 values of 20.26 and 3.88 μM at 24 and 48 h, respectively. Against amastigote forms, the IC 50 value of LicoA was 36.84 μM at 48 h. In the next step, the effectivity of LicoA was evaluated in vitro against promastigote and amastigote forms of L. (L.) infantum . Results demonstrated that LicoA exhibited leishmanicidal activity in vitro against promastigote forms with IC 50 values of 41.10 and 12.47 μM at 24 and 48 h, respectively; against amastigote forms the IC 50 value was 29.58 μM at 48 h. Assessment of cytotoxicity demonstrated that LicoA exhibited moderate mammalian cytotoxicity against peritoneal murine macrophages; the CC 50 value was 123.21 μM at 48 h and showed about 30% of hemolytic activity at concentration of 400 μM. L. (L.) infantum- infected hamsters and treated with LicoA at 50 mg/kg for eight consecutive days was able to significantly reduce the parasite burden in both liver and spleen in 43.67 and 39.81%, respectively, when compared with negative control group. These findings suggest that chalcone-type flavonoids can be a promising class of natural products to be considered in the search of new, safe, and effective compounds capable to treat canine visceral leishmaniosis (CVL)., 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 © 2020 Souza, de Carvalho, Candido, de Mendonça, Fernanda da Silva, Parreira, Dias, Ambrósio, Arantes, da Silva Filho, Nascimento, Costa, Sairre, Veneziani and Magalhães.)

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., Competing Interests: Declaration of Competing Interest The authors reported no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Nectandra megapotamica is a tree species that naturally occurs in the Atlantic Forest, Brazil. This paper aims to investigate the chemical composition and in vitro antibacterial, antileishmanial and antiproliferative activities of essential oil from N. megapotamica leaves (NM-EO). It displayed high antibacterial activity against Streptococcus mutans , S. sobrinus, Prevotella nigrescens and Bacteroides fragilis . NM-EO also exhibited high antileishmanial activity against promastigote forms of Leishmania amazonensis . Its antiproliferative activity was evaluated against the following cells: GM07429A (normal cell), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma) and M059J (human glioblastoma). Its major components, which were determined by GC-FID and GC-MS, were α-bisabolol (13.7%), bicyclogermacrene (10.9%), ( E , E )-farnesene (10.6%), Z -caryophyllene (9.5%) and ( E )-β-farnesene (7.0%). These results suggest that N. megapotamica , a Brazilian plant, shows initial evidence of a new and alternative source of substances of medicinal interest.

Here, we describe the chemical synthesis and biological activity of a new Doxycycline derivative, designed specifically to more effectively target cancer stem cells (CSCs). In this analog, a myristic acid (14 carbon) moiety is covalently attached to the free amino group of 9-amino-Doxycycline. First, we determined the IC 50 of Doxy-Myr using the 3D-mammosphere assay, to assess its ability to inhibit the anchorage-independent growth of breast CSCs, using MCF7 cells as a model system. Our results indicate that Doxy-Myr is >5-fold more potent than Doxycycline, as it appears to be better retained in cells, within a peri-nuclear membranous compartment. Moreover, Doxy-Myr did not affect the viability of the total MCF7 cancer cell population or normal fibroblasts grown as 2D-monolayers, showing remarkable selectivity for CSCs. Using both gram-negative and gram-positive bacterial strains, we also demonstrated that Doxy-Myr did not show antibiotic activity, against Escherichia coli and Staphylococcus aureus . Interestingly, other complementary Doxycycline amide derivatives, with longer (16 carbon; palmitic acid) or shorter (12 carbon; lauric acid) fatty acid chain lengths, were both less potent than Doxy-Myr for the targeting of CSCs. Finally, using MDA-MB-231 cells, we also demonstrate that Doxy-Myr has no appreciable effect on tumor growth, but potently inhibits tumor cell metastasis in vivo , with little or no toxicity. In summary, by using 9-amino-Doxycycline as a scaffold, here we have designed new chemical entities for their further development as anti-cancer agents. These compounds selectively target CSCs, e.g., Doxy-Myr, while effectively minimizing the risk of driving antibiotic resistance. Taken together, our current studies provide proof-of-principle, that existing FDA-approved drugs can be further modified and optimized, to successfully target the anchorage-independent growth of CSCs and to prevent the process of spontaneous tumor cell metastasis., (Copyright © 2020 Ózsvári, Magalhães, Latimer, Kangasmetsa, Sotgia and Lisanti.)

The chemotherapy of schistosomiasis remains centered in the use of praziquantel, however, there has been growing resistant parasites to this drug. Thus, the aim of this work was to evaluate in vitro schistosomicidal activity of the hexanes/dichloromethane 1 : 1 extract of Brazilian green propolis (Pex), as well as its major isolated compounds artepillin C, caffeic acid, coumaric acid and drupanin against Schistosoma mansoni. The Pex was active by displaying an IC 50 value of 36.60 (26.26-51.13) μg mL -1 at 72 h against adult worms of S. mansoni. The major isolated compounds were inactive with IC 50 values >100 μM, however, the combination of the isolated compounds (CM) in the same range found in the extract was active with an IC 50 value of 41.17 (39.89-42.46) μg mL -1 at 72 h. Pex and CM induced alteration in the tegument of S. mansoni, and caffeic acid caused alteration in egg's maturation. Pex displayed in vitro activity against adult worms' and eggs' viability of S. mansoni, which opens new perspectives to better understand the synergistic and/or additive effects promoted by both Pex extract and CM against schistosomiasis features., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

The proteasome is the key player in the cellular protein degradation machinery and is pivotal for protein homeostasis and Schistosoma mansoni (S. mansoni) survival. Our group study provides insights into proteasome inhibitors and reveals that selective schistosomiasis agents represent an interesting branch of proteasome research linked to the development of new drugs for this neglected disease. Here, we explored the phenotypic response of S. mansoni to b-AP15, a bis-benzylidine piperidone that inhibits 26S proteasome deubiquitinases (DUBs), ubiquitin-specific protease 14 (USP14), and ubiquitin carboxyl-terminal hydrolase 5 (UCHL5). b-AP15 induces a modest decrease in egg production in vitro and reduces viability, leading to the death of parasite couples. This inhibitor also induces a twofold increase in the accumulation of polyubiquitinated proteins in S. mansoni adult worms and causes tegument changes such as disintegration, wrinkling, and bubble formation, both throughout the length of the parasite and in the oral sucker. b-AP15 alters the cell organelles of adult S. mansoni worms, and we specifically observed mitochondrial alterations, which are suggestive of proteotoxic stress leading to autophagy. Taken together, these results indicate that the deubiquitinase function of the proteasome is essential for the parasite and support the hypothesis that the proteasome constitutes an interesting drug target for the treatment of schistosomiasis.

Background: Schistosomiasis control in endemic areas depends on several factors, including chemotherapy, snail control and adequate sanitation. In this context, the employment of compounds isolated from plants is an important issue regarding infection and snail control. The aim of this study was therefore to evaluate the effects of curcumin (CUR), a compound isolated from Curcuma longa, against snails and embryos of Biomphalaria glabrata, which is the most important intermediate host of schistosomiasis in the Americas, as well as in cercariae, the infecting larval stage of Schistosoma mansoni., Results: CUR presented high activity against B. glabrata embryos and moderate activity against newborn and adult snails. The lethal concentration (LC 50 ) values after being exposed for 24 h and evaluated for 7 days were 6.54 (95% confidence interval (CI) 5.86-7.30) μg mL -1 for the embryos and 42.29 (95% CI 33.82-52.87) μg mL -1 and 87.69 (95% CI 68.82-111.7) μg mL -1 for the newborn and adult snails, respectively. Moreover, CUR inhibited the development of embryos and egg hatching, and decreased the fecundity rates of adult snails. CUR also demonstrated cercaricidal activity with LC 50 values lower than 10 μg mL -1 at 1, 3, 6, 9 and 12 h, respectively., Conclusion: Our data show that CUR has potential molluscicidal and cercaricidal activities. Moreover, as a nutraceutical compound that is toxic to both invertebrate host and parasite, CUR has the potential to be explored as a safe new agent to combat schistosomiasis. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

A virtual screening conducted with nearly 4 000 000 compounds from lead-like and fragment-like subsets enabled the identification of a small-molecule inhibitor ( 1 ) of the Trypanosoma cruzi cruzain enzyme, a validated drug target for Chagas disease. Subsequent comprehensive structure-based drug design and structure-activity relationship studies led to the discovery of carbamoyl imidazoles as potent, reversible, and competitive cruzain inhibitors. The most potent carbamoyl imidazole inhibitor ( 45 ) exhibited high affinity with a K i value of 20 nM, presenting both in vitro and in vivo activity against T. cruzi . Furthermore, the most promising compounds reduced parasite burden in vivo and showed no toxicity at a dose of 100 mg/kg. These carbamoyl imidazoles are structurally attractive, nonpeptidic, and easy to prepare and synthetically modify. Finally, these results further advance our understanding of the noncovalent mode of inhibition of this pharmaceutically relevant enzyme, building strong foundations for drug discovery efforts.

Electrochemical synthesis has been presented as a powerful technique to produce nanoparticles. However, it has been especially focused on noble metal particles, while few studies have been done on oxides production. On the other hand, when partially doped with trivalent cations at the barium sublattice, BaTiO₃-based ceramics are well known to exhibit semiconductive character, accompanied by a positive temperature coefficient of resistivity (PTCR). Here, we synthesized pure and La-doped BaTiO₃ nanoparticles electrochemically using a metallic titanium electrode as a Ti source. The powder synthesis was made in an electrochemical cell coupled to a thermostatic bath under mild conditions (ambient temperature and pressure) with an electrical potential up to 50 V and current of 3.2 A. In these conditions, the synthesized powders present nanometric size, confirmed by transmission electron microscopy images. The pseudo-cubic BaTiO₃ phase is confirmed by X-ray diffraction and Raman spectroscopy techniques. To check the quality, the powders were sintered at 1250 °C and the ceramics achieved a relative density of 95%. The BaTiO₃:La sintered ceramics present a PTCR jump of up to three orders of magnitude on resistivity with minimum value at room temperature of 10 5 Ω·cm.

This paper reports the synthesis of (±)-licarin A 1, a dihydrobenzofuran neolignan, resultant of an oxidative coupling reaction of isoeugenol and horseradish peroxidase (HRP) enzyme. Following, three semi-synthetic derivatives from this compound were obtained: benzylated (±)-licarin A 2, methylated (±)-licarin A 3 and acetylated (±)-licarin A 4. After structural elucidation and assignment by Nuclear Magnetic Resonance of 1 H, 13 C and DEPT, all compounds were evaluated in vitro against Trypomastigote forms of Trypanosoma cruzi (T. cruzi), the etiologic agent of Chagas disease, and Schistosoma mansoni (S. mansoni) worms, the etiologic agent of schistosomiasis. Compound (4) was the most active against S. mansoni adult worms, displaying worm viability reduction at 25 µM and mortality of all worms at 100 and 200 µM within 24 h. Compound 1 was the second most active, showing worm viability reduction at 50 µM and mortality of 25% and 100% of worms in 24h at concentrations of 100 and 200 µM, respectively. In addition, theoretical calculations aiming at finding molecular properties that showed the correlation for schistosomicidal and trypanocidal activities of (±)-licarin A and three of its semi-synthetic derivatives were also performed., Competing Interests: Conflict of Competing Interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Chagas disease causes ~10,000 deaths each year, mainly in Latin America, where it is endemic. The currently available chemotherapeutic agents are ineffective in the chronic stage of the disease, and the lack of pharmaceutical innovation for Chagas disease highlights the urgent need for the development of new drugs. The enzyme cruzain, the main cysteine protease of Trypanosoma cruzi , has been explored as a validated molecular target for drug discovery. Herein, the design, molecular modeling studies, synthesis, and biological evaluation of cyclic imides as cruzain inhibitors are described. Starting with a micromolar-range cruzain inhibitor ( 3a , IC 50 = 2.2 μM), this molecular optimization strategy resulted in the nanomolar-range inhibitor 10j (IC 50 = 0.6 μM), which is highly active against T. cruzi intracellular amastigotes (IC 50 = 1.0 μM). Moreover, most compounds were selective toward T. cruzi over human fibroblasts, which were used as host cells, and are less toxic to hepatic cells than the marketed drug benznidazole. This study enabled the discovery of novel chemical diversity and established robust structure-activity relationships to guide the design of optimized cruzain inhibitors as new trypanocidal agents., (Copyright © 2019 Ferreira, Pauli, Sampaio, de Souza, Ferreira, Magalhães, Rezende, Ferreira, Krogh, Dias and Andricopulo.)

Eugenia species have been appreciated for their edible fruits and medicinal properties. This paper aims to investigate the chemical composition and in vitro antileishmanial, antifungal and antiproliferative activities of essential oil from aerial parts of Eugenia pyriformis (EP-EO). The oil showed strong antileishmanial activity against promastigote forms of Leishmania amazonensis (IC 50 = 2.16 µg/mL). It also exhibited high antifungal activity against Malassezia furfur (MIC = 30 µg/mL), which was determined by the broth microdilution method. Its antiproliferative activity was evaluated against the following cells: GM07429A (normal cell), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma) and M059J (human glioblastoma). Its major constituents, which were determined by GC-FID and GC-MS, were limonene (14.8%), nerolidol (11.0%), α-cadinol (10.3%), caryophyllene oxide (9.9%) and β-pinene (7.1%). These results showed, for the first time, the effectiveness of EP-EO as a natural product which has promising biological activities, a fact that enables its ethnopharmacological use.

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 (IC 50 < 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., (Copyright © 2019 Vigato, Querobino, de Faria, Candido, Magalhães, Cereda, Tófoli, Campos, Machado, Fraceto, de Sairre and de Araujo.)

Six dibenzylbutyrolactonic lignans ((-)-hinokinin (1), (-)-cubebin (2), (-)-yatein (3), (-)-5-methoxyyatein (4), dihydrocubebin (5) and dihydroclusin (6)) were isolated from Piper cubeba seed extract and evaluated against Schistosoma mansoni. All lignans, except 5, were able to separate the adult worm pairs and reduce the egg numbers during 24 h of incubation. Lignans 1, 3 and 4 (containing a lactone ring) were the most efficient concerning antiparasitary activity. Comparing structures 3 and 4, the presence of the methoxy group at position 5 appears to be important for this activity. Considering 1 and 3, it is possible to see that the substitution pattern change (methylenedioxy or methoxy groups) in positions 3' and 4' alter the biological response, with 1 being the second most active compound. Computational calculations suggest that the activity of compound 4 can be correlated with the largest lipophilicity value., (© 2019 Wiley-VHCA AG, Zurich, Switzerland.)

We investigate the chemical composition and the in vitro antileishmanial and cytotoxic activities of the essential oils extracted from the leaves of Ocotea dispersa (Nees) Mez (OD-EO) and Ocotea odorifera (Vell) Rohwer (OO-EO). On the basis of GC-FID and GC-MS, α-eudesmol (20.9%), valencene (10.2%), δ-elemene (9.3%) and isospathulenol (7.3%) are the major constituents of OD-EO, whereas safrole (36.3%), γ-cadinene (6.6%), camphor (6.5%) and α-copaene (6.0%) are the main constituents of OO-EO. Both OD-EO and OO-EO display significant activity against the promastigote forms of Leishmania amazonensis , with IC 50 values of 4.67 ± 0.95 and 11.67 ± 2.16 μg/mL, respectively. The 50% cytotoxic concentration (CC 50 ) of OD-EO and OO-EO to mouse peritoneal macrophages is 26.77 ± 4.06 and 49.52 ± 1.04 μg/mL, respectively. This is the first report on the chemical composition of the essential oil extracted from the leaves of O. dispersa . Our results suggest that OD-EO and OO-EO are a promising source of new antileishmanial agents.

Aim: To evaluate the antibacterial activity of 12 kaurane-type diterpenes against a panel of bacteria that cause endodontic infection., Methods & Materials: We conducted tests against bacteria in the planktonic or in the sessile mode, cytotoxic assays for the most promising compounds against human normal lung fibroblast cells, and Porphyromonas gingivalis (ATCC 33277) proteomic analysis., Results & Conclusion: Kaurenoic acid and its salt exhibited satisfactory antibacterial action against the evaluated bacteria. Proteomic analysis suggested that these compounds might interfere in bacterial metabolism and virulence factor expression. Kaurane-type diterpenes are an important class of natural products and should be considered in the search for new irrigating solutions to treat endodontic infections.

Leishmaniasis is an endemic disease caused by protozoa of the genus Leishmania, which affects around two million people worldwide. One major drawback in the treatment of leishmaniasis is the emergence of resistance to current chemotherapeutics. Medicinal and aromatic plants constitute a major source of natural organic compounds. In this study, the leaf essential oil of Cryptocarya aschersoniana was obtained by hydrodistillation in a Clevenger-type apparatus, and the chemical composition was analyzed by GC-MS and GC-FID. The essential oil of these species was predominantly constituted by monoterpene hydrocarbons (48.8%). Limonene (42.3%), linalool (9.7%) and nerolidol (8.6%) were the main constituents in the oil of C. aschersoniana. The in vitro activity of the oil was evaluated against the promastigote forms of Leishmania amazonensis, the causative agent of cutaneous leishmaniasis in humans. The essential oil of C. aschersoniana showed high activity against L. amazonensis promastigote forms (IC50 = 4.46 µg/mL), however, it also demonstrated a relatively high cytotoxicity on mouse peritoneal macrophages (CC50 = 7.71 µg/mL). This is the first report of the chemical composition and the leishmanicidal and cytotoxic activities of the leaf essential oil of C. aschersoniana.

We have evaluated the antischistosomal activity of synthetic dihydrobenzofuran neolignans (DBNs) derived from (±)-trans-dehydrodicoumaric acid dimethyl ester (1) and (±)-trans-dehydrodiferulic acid dimethyl ester (2) against adult Schistosoma mansoni worms in vitro. Compound 4 ((±)-trans-4-O-acetyldehydrodiferulic acid dimethyl ester) displayed the most promising activity; at 200 μm, it kills 100 ± 0% of worms after 24 h, which resembles the result achieved with praziquantel (positive control) at 1.56 μm. The hydrogenation of the double bond between C7' and C8', the introduction of an additional methyl group at C3', and a double bond between C7 and C8 decreased the schistosomicidal activity of DBNs. On the other hand, the presence of the acetoxy group at C4 played an interesting role in this activity. These results demonstrated the interesting schistosomicidal potential of DBNs, which could be further exploited., (© 2018 Wiley-VHCA AG, Zurich, Switzerland.)

Two new bracelet cyclotides from roots of Pombalia calceolaria with potential anticancer activity have been characterized in this work. The cyclotides Poca A and B (1 and 2) and the previously known CyO4 (3) were de novo sequenced by MALDI-TOF/TOF mass spectrometry (MS). The MS 2 spectra were examined and the amino acid sequences were determined. The purified peptides were tested for their cytotoxicity and effects on cell migration of MDA-MB-231, a triple-negative breast cancer cell line. The isolated cyclotides reduced the number of cancer cells by more than 80% at 20 μM, and the concentration-related cytotoxic responses were observed with IC 50 values of 1.8, 2.7, and 9.8 μM for Poca A (1), Poca B (2), and CyO4 (3), respectively. Additionally, the inhibition of cell migration (wound-healing assay) exhibited that CyO4 (3) presents an interesting activity profile, in being able to inhibit cell migration (50%) at a subtoxic concentration (2 μM). The distribution of these cyclotides in the roots was analyzed by MALDI imaging, demonstrating that all three compounds are present in the phloem and cortical parenchyma regions.

Context: (-)-6,6'-Dinitrohinokinin (DNHK) display remarkable antiparasitic activity and was, therefore, incorporated into a nanoparticle formulation., Objective: Incorporation of DNHK in poly lactic-co-glycolic acid (PLGA) nanoparticles aiming to improve its biological activities., Materials and Methods: Synthesis, characterization and incorporation of DNHK into glycolic acid (PLGA) nanoparticles by nanoprecipitation method. The nanoparticles were characterized by ultraviolet-visible spectroscopy, X-ray diffraction, field emission electron microscopic scanning mansoni (FESEM), and dynamic light scattering (DLS). For the in vitro test with Schistosoma mansoni, the DNHK-loaded PLGA was diluted into the medium, and added at concentrations 10-200 µM to the culture medium containing one adult worm pair. The parasites were kept for 120 h and monitored every 24 h to evaluate their general condition, including: pairing, alterations in motor activity and mortality., Results: The loaded PLGA nanoparticles gave an encapsulation efficiency of 42.2% and showed spherical characteristics in monodisperse polymeric matrix. The adult worm pairs were separated after 120 h of incubation for concentrations higher than 50 µM of DNHK-loaded PLGA. The groups incubated with 150 and 200 µM of DNHK-loaded PLGA for 24 and 120 h killed 100% of adult worms, afforded LC 50 values of 137.0 ± 2.12 µM and 79.01 ± 1.90 µM, respectively, which was similar to the effect displayed by 10 µM of praziquantel., Discussion and Conclusions: The incorporation of DNHK-loaded showed schistosomicidal activity and allowed its sustained release. The loaded PLGA system can be administered intravenously, as well as it may be internalized by endocytosis by the target organisms.

This paper is the first report on the in vitro effects of licochalcone A, a chalcone isolated from Glycyrrhiza inflate Batalin (Leguminosae), on Schistosoma mansoni adult worms. In vitro, licochalcone A afforded lethal concentrations for 50% of parasites (LC 50 ) of 9.12±1.1 and 9.52±0.9μM against female and male adult worms, respectively, at 24h. Additionally, the compound reduced the total number of S. mansoni eggs and affected the development of eggs produced by S. mansoni adult worms. Together, the results achieved after 24h showed that licochalcone A was 55.7- and 53.3-fold more toxic to S. mansoni female and male adult worms than to Chinese hamster ovary fibroblasts cells, respectively. Treatment with licochalcone A elicited drastic changes in the tegument of S. mansoni adult worms, as well as mitochondrial alteration and chromatin condensation. Licochalcone A also increased the superoxide anion level and decreased the superoxide dismutase activity in S. mansoni adult worms. Overall, our results indicated that licochalcone A displays in vitro schistosomicidal activity. This effect may result from increased production of reactive oxygen species (ROS) induced by the action of licochalcone A. The resulting ROS could act on the S. mansoni tegument and membranes and help induce the death of S. mansoni adult worms., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)