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

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

Abstract 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

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

<p>We investigate the chemical composition and the <i>in vitro</i> antileishmanial and cytotoxic activities of the essential oils extracted from the leaves of <i>Ocotea dispersa</i> (Nees) Mez (OD-EO) and <i>Ocotea odorifera</i> (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 <i>Leishmania amazonensis</i>, 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 <i>O. dispersa</i>. Our results suggest that OD-EO and OO-EO are a promising source of new antileishmanial agents.</p

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

<div><p>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.</p></div