Metabolite profile of Nectandra oppositifolia Nees & Mart. and assessment of antitrypanosomal activity of bioactive compounds through efficiency analyses

Abstract

EtOH extracts from the leaves and twigs of Nectandra oppositifolia Nees & Mart. shown activity against amastigote forms of Trypanosoma cruzi. These extracts were subjected to successive liquid-liquid partitioning to afford bioactive CH2Cl2 fractions. UHPLC-TOF-HRMS/MS and molecular networking were used to obtain an overview of the phytochemical composition of these active fractions. Aiming to isolate the active compounds, both CH2Cl2 fractions were subjected to fractionation using medium pressure chromatography combined with semi-preparative HPLC-UV. Using this approach, twelve compounds (1–12) were isolated and identified by NMR and HRMS analysis. Several isolated compounds displayed activity against the amastigote forms of T. cruzi, especially ethyl protocatechuate (7) with EC50 value of 18.1 μM, similar to positive control benznidazole (18.7 μM). Considering the potential of compound 7, protocatechuic acid and its respective methyl (7a), n-propyl (7b), n-butyl (7c), n-pentyl (7d), and n-hexyl (7e) esters were tested. Regarding antitrypanosomal activity, protocatechuic acid and compound 7a were inactive, while 7b-7e exhibited EC50 values from 20.4 to 11.7 μM, without cytotoxicity to mammalian cells. These results suggest that lipophilicity and molecular complexity play an important role in the activity while efficiency analysis indicates that the natural compound 7 is a promising prototype for further modifications to obtain compounds effective against the intracellular forms of T. cruzi.

Simplified Derivatives of Dibenzylbutyrolactone Lignans from Hydrocotyle bonariensis as Antitrypanosomal Candidates

“… [51] As indicated in Table 2, values of ClogP (logarithm of n ‐octanol/water), Fsp 3 (fraction of sp 3 carbons), HBD (hydrogen bond donor), HBA (hydrogen bond acceptor), MW (molecular weight), TPSA (topological polar surface area), rotatable bonds, and water solubility were calculated. Other parameters such as the values of gastrointestinal (GI) absorption, blood‐brain barrier penetration (BBB permeant), the potential to inhibit CYP1A2 isoforms and the presence of pan‐assay interference sub‐structures (PAINS) were determined as previously described [7] …”

“…Other parameters such as the values of gastrointestinal (GI) absorption, blood-brain barrier penetration (BBB permeant), the potential to inhibit CYP1A2 isoforms and the presence of pan-assay interference sub-structures (PAINS) were determined as previously described. [7] Statistical Analysis EC 50 and CC 50 values represent the mean of three independent representative assays tested in duplicate and were calculated using a sigmoid dose-response curves in Graph-Pad Prism 5.0 software (GraphPad Prism software 6.0, San Diego, CA, USA). Lethal action studies were analyzed using ANOVA test turkey for significance (p < 0.05).…”

“…Currently, the therapy of CD is only focused in two drugs – nifurtimox and benznidazole – with severe adverse side effects and reduced effectiveness [5–6] . Therefore, the search for new therapeutic alternatives for CD consists in an urgent need and natural products consists an important start point for development of new drugs [7] …”

“…[5 -6] Therefore, the search for new therapeutic alternatives for CD consists in an urgent need and natural products consists an important start point for development of new drugs. [7] Distributed in tropical and temperate regions, [8,9] plants belonging to Hydrocotyle genus (Araliaceae) have been used in Taiwan folk medicine for treatment of dysentery, zoster, cold, inflammatory impairments, eczema, and pain relief. [10] In Brazil, Hydrocotyle bonariensis Lam.…”

Anti-Neuroinflammatory Potential of a Nectandra angustifolia (Laurel Amarillo) Ethanolic Extract

“…Nees & Mart., popularly called "yellow laurel", "river laurel" or "aju'y hû", is a native plant that can be found largely in Argentina, Brazil, and Uruguay [13]. Some species of the genus Nectandra have been used in folk medicine as digestives, purgatives and antispasmodics and for treatment of rheumatism, arthritis and pain [14][15][16]. Moreover, local inhabitants use leaves to ameliorate the local inflammatory effects caused by venomous snake bites [17].…”