Exploring Synthetic Dihydrobenzofuran and Benzofuran Neolignans as Antiprotozoal Agents against Trypanosoma cruzi.

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 (IC50 from 7.96 to 21.12 µM), and DBN 1 exhibited the highest activity against the amastigote forms of the T. cruzi Y strain (IC50 3.26 µM). Compounds 1-4 showed CC50 values higher than antitrypanosomal activities, except for DBN 3. All DBNs with antitrypanosomal activity demonstrated CH50 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.

Brazilian green propolis reduces worm burden and hepatic granuloma formation in a Schistosoma mansoni experimental murine model.

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.

Antischistosomal Activity of Essential Oils: An Updated Review.

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.

In vitro anti-trypanosomal potential of kaurane and pimarane semi-synthetic derivatives.

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 IC50 <12.5 µM (estimated 0.8 µM), lower than Benznidazole (IC50 = 9.8 µM), used as control. The esterification of acid diterpenes showed to be an interesting way in the search for anti-trypanosomal agents.

Trypanocidal Activity of Dysphania ambrosioides, Lippia alba, and Tetradenia riparia Essential Oils against Trypanosoma cruzi.

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 IC50 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.

Uncovering Biological Application of Brazilian Green Propolis: A Phenotypic Screening against Schistosoma mansoni.

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 IC50 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 IC50 values >100 µM, however, the combination of the isolated compounds (CM) in the same range found in the extract was active with an IC50 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.

Chemical composition and evaluation of antileishmanial and cytotoxic activities of the essential oil from leaves of Cryptocarya aschersoniana Mez. (Lauraceae Juss.).

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.

Schistosomicidal Activity of Dihydrobenzofuran Neolignans.

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.

Chemical composition and in vitro antileishmanial and cytotoxic activities of the essential oils of Ocotea dispersa (Nees) Mez and Ocotea odorifera (Vell) Rohwer (Lauraceae).

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 IC50 values of 4.67 ± 0.95 and 11.67 ± 2.16 µg/mL, respectively. The 50% cytotoxic concentration (CC50) 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.

In vitro antiparasitic activity and chemical composition of the essential oil from Protium ovatum leaves (Burceraceae)

ABSTRACT Leishmaniasis and trypanosomiasis are globally widespread parasitic diseases which have been responsible for high mortality rates. Since drugs available for their treatment are highly hepatotoxic, nephrotoxic and cardiotoxic, adherence to therapy has been affected. Thus, the search for new, more effective and safer drugs for the treatment of these diseases is necessary. Natural products have stood out as an alternative to searching for new bioactive molecules with therapeutic potential. In this study, the chemical composition and antiparasitic activity of the essential oil from Protium ovatum leaves against trypomastigote forms of Trypanosoma cruzi and the promastigote forms of Leishmania amazonensis were evaluated. The essential oil was promising against trypomastigote forms of T. cruzi (IC50= 28.55 μg.mL-1) and L. amazonensis promastigotes (IC50 = 2.28 μg.mL-1). Eighteen chemical constituents were identified by Gas Chromatography coupled to Mass Spectrometry (GC-MS) in the essential oil, whose major constituents were spathulenol (17.6 %), caryophyllene oxide (16.4 %), β-caryophyllene (14.0 %) and myrcene (8.4 %). In addition, the essential oil from P. ovatum leaves had moderate cytotoxicity against LLCMK2 adherent epithelial cell at the concentration range under analysis (CC50 = 150.9 μg.mL-1). It should be highlighted that this is the first report of the chemical composition and anti-Trypanosoma cruzi and anti-Leishmania amazonensis activities of the essential oil from Protium ovatum leaves.

In vitro antiparasitic activity and chemical composition of the essential oil from Protium ovatum leaves (Burceraceae).

Leishmaniasis and trypanosomiasis are globally widespread parasitic diseases which have been responsible for high mortality rates. Since drugs available for their treatment are highly hepatotoxic, nephrotoxic and cardiotoxic, adherence to therapy has been affected. Thus, the search for new, more effective and safer drugs for the treatment of these diseases is necessary. Natural products have stood out as an alternative to searching for new bioactive molecules with therapeutic potential. In this study, the chemical composition and antiparasitic activity of the essential oil from Protium ovatum leaves against trypomastigote forms of Trypanosoma cruzi and the promastigote forms of Leishmania amazonensis were evaluated. The essential oil was promising against trypomastigote forms of T. cruzi (IC50= 28.55 µg.mL-1) and L. amazonensis promastigotes (IC50 = 2.28 µg.mL-1). Eighteen chemical constituents were identified by Gas Chromatography coupled to Mass Spectrometry (GC-MS) in the essential oil, whose major constituents were spathulenol (17.6 %), caryophyllene oxide (16.4 %), ß-caryophyllene (14.0 %) and myrcene (8.4 %). In addition, the essential oil from P. ovatum leaves had moderate cytotoxicity against LLCMK2 adherent epithelial cell at the concentration range under analysis (CC50 = 150.9 µg.mL-1). It should be highlighted that this is the first report of the chemical composition and anti-Trypanosoma cruzi and anti-Leishmania amazonensis activities of the essential oil from Protium ovatum leaves.