Antileishmanial activity and ultrastructural changes of related tetrahydrofuran dineolignans isolated from Saururus cernuus L. (Saururaceae)

Abstract

Objective This work describes the isolation of anti-Leishmania amazonensis metabolites from Saururus cernuus (Saururaceae). Additionally, ultrastructural changes in promastigotes were evidenced by electron microscopy. Methods The MeOH extract from the leaves of S. cernuus was subjected to bioactivity-guided fractionation. Anti-L. amazonensis activity of purified compounds was performed in vitro against promastigote and amastigote forms. Key findings Bioactivity-guided fractionation of the MeOH extract from the leaves of S. cernuus afforded two related tetrahydrofuran dineolignans: threo, threo-manassantin A (1) and threo,erythro-manassantin A (2). Compounds 1 and 2 displayed activity against promastigotes (EC 50 of 35.4 AE 7.7 and 17.6 AE 4.2 lM, respectively) and amastigotes (EC 50 of 20.4 AE 1.9 and 16.0 AE 1.1 lM, respectively), superior to that determined for the positive control miltefosine (EC 50 of 28.7 AE 3.5 lM). Reduced cytotoxicity for host cells was observed for both compounds. Additionally, ultrastructural changes in promastigotes leading to an alteration of structural morphology were observed, as evidenced by electron microscopy. Furthermore, these compounds altered the morphology and physiology of the plasmatic membrane of L. amazonensis. Conclusions The obtained results indicated that dineolignans 1 and 2 could be considered as a scaffold for the design of novel and selective drug candidates for the treatment of leishmaniasis.

Mechanistic Insights into the Leishmanicidal and Bactericidal Activities of Batroxicidin, a Cathelicidin-Related Peptide from a South American Viper (Bothrops atrox)

“…To assess the effect of peptides on Leishmania membrane integrity, SYTOX Green assays were conducted (Figure 3B). This probe enters cells following membrane disruption and becomes fluorescent upon interaction with the DNA 36 (Figure 3C). We verified that the three peptides altered the parasite cell membrane over time, with BatxC(C-2.15Phe) being the most active at changing the integrity of the parasite membrane at both concentrations tested (EC 50 and 2 × EC 50 ) (Figure 3D).…”

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“…A considerable number of plant secondary metabolites have anti-protozoal activity (Gervazoni et al, 2020;Oryan, 2015;Schmidt et al, 2012aSchmidt et al, , 2012bRandhawa et al, 2011;Mehwish et al, 2019). The alternative systems of herbal medicine have been used since ancient times and different extracts of medicinal plants and herbal formulations have demonstrated potential for use in Leishmaniasis such as plant lignans, neolignans, and Quinones, Alkaloids, Flavonoids, and Terpenoids (Maia et al, 2020;Gervazoni et al, 2020;Rodrigues et al, 2016;De Castro Oliveira et al, 2017;Saha et al, 2013;Chowdhury et al, 2012;Brito et al, 2019). Coumarins are derivatives that have a hydroxyl group, which differs in their biological properties.…”

“…This plant extracts were also tested against Leishmania amazonensis promastigote, and showed anti-leishmania activity (Gervazoni et al, 2020). Two neolignans, threomanassantin A and erythro-manassantin A, isolated from Saururus cernuus exhibited activity against promastigotes (IC50 of 35.4 and 17.6 μM, respectively) and intracellular amastigotes (IC50 of 20.4 and 16.0μM, respectively) of Leishmania amazonensis (Gervazoni et al, 2020;Brito et al, 2019). Both molecules were determined to be able to interact with the parasite plasmatic membrane and to interfere with the parasite nucleus (Gervazoni et al, 2020;Brito et al, 2019).…”

“…Two neolignans, threomanassantin A and erythro-manassantin A, isolated from Saururus cernuus exhibited activity against promastigotes (IC50 of 35.4 and 17.6 μM, respectively) and intracellular amastigotes (IC50 of 20.4 and 16.0μM, respectively) of Leishmania amazonensis (Gervazoni et al, 2020;Brito et al, 2019). Both molecules were determined to be able to interact with the parasite plasmatic membrane and to interfere with the parasite nucleus (Gervazoni et al, 2020;Brito et al, 2019). In another study, caffeic acid has leishmanicidal effects with a mechanism of action that triggers multiple targets that affect the viability of the parasite (Gervazoni et al, 2020;Bortoleti et al, 2019;Garcia et al, 2019).…”

Use of Natural Products in Leishmaniasis Chemotherapy: An Overview

“…Regardless of the mode of action, these compounds seem to act directly on parasites, since host cells did not show signs of cell activation. Both molecules were determined to be able to interact with the parasite plasmatic membrane and to interfere with the parasite nucleus (Brito et al, 2019).…”