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Schistosomiasis, a parasitic disease caused by the blood fluke of the genus Schistosoma, affects over 230 million people, especially in developing countries. Despite the significant economic and public health consequences, only one drug is currently available for treatment of schistosomiasis, praziquantel. Thus, there is an urgent demand for new anthelmintic agents. Based on our continuous studies involving the chemical prospection of floristic biodiversity aiming to discover new bioactive compounds, this work reports the in vitro antiparasitic activity against Schistosoma mansoni adult worms of neolignans threo-austrobailignan-6 and verrucosin, both isolated from Saururus cernuus L. (Saururaceae). These neolignans showed a significant in vitro schistosomicidal activity, with EC50 values of 12.6–28.1 µM. Further analysis revealed a pronounced reduction in the number of S. mansoni eggs. Scanning electron microscopy analysis revealed morphological alterations when schistosomes were exposed to either threo-austrobailignan-6 or verrucosin. These relevant antischistosomal properties were accompanied by low cytotoxicity potential against the animal (Vero) and human (HaCaT) cell lines, resulting in a high selectivity index. Considering the promising chemical and biological properties of threo-austrobailignan-6 and verrucosin, this research should be of interest to those in the area of neglected diseases and in particular antischistosomal drug discovery.

Bioactivity-guided fractionation of the separate CH2Cl2 extracts from the aerial parts of Peperomia alata and P. trineura yielded seven polyketides: alatanone A [3-hydroxy-2-(5'-phenylpent-4'E-enoyl)cyclohex-2-en-1-one, 1a] and alatanone B [3-hydroxy-2-(3'-phenyl-6'-methylenedioxypropanoyl)cyclohex-2-en-1-one, 2a] from P. alata and trineurone A [3-hydroxy-2-(11'-phenylundec-10'E-enoyl)cyclohex-2-en-1-one, 1b], trineurone B [3-hydroxy-2-(15'-phenyl-18'-methylenedioxypentadecanoyl)cyclohex-2-en-1-one, 2b], trineurone C [3-hydroxy-2-(17'-phenyl-20'-methylenedioxyheptadecanoyl)cyclohex-2-en-1-one, 2c], trineurone D [3-hydroxy-2-(hexadec-10'Z-enoyl)cyclohex-2-en-1-one, 3a], and trineurone E [(6R)-(+)-3,6-dihydroxy-2-(hexadec-10'Z-enoyl)cyclohex-2-en-1-one, 3b] from P. trineura. The isolated compounds were evaluated for antifungal activity against Cladosporium cladosporioides and C. sphaeospermum and for cytotoxicity against the K562 and Nalm-6 leukemia cell lines.

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.

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