Evaluating the Antischistosomal Activity of Dehydrodieugenol B and Its Methyl Ether Isolated from Nectandra leucantha-A Preclinical Study against Schistosoma mansoni Infection.

Schistosomiasis, a parasitic disease affecting nearly 250 million individuals globally, poses a significant health challenge. With praziquantel being the sole available treatment and its limited efficacy in early stage infections, the identification of novel bioactive compounds becomes imperative. This study examines the potential of dehydrodieugenol B (1) and its methyl ether (2), derived from the leaves of the Brazilian Nectandra leucantha plant (Lauraceae), in combatting Schistosoma mansoni infections through a preclinical approach. Initially, compound 1 displayed noteworthy in vitro antiparasitic activity with an EC50 of 31.9 µM, showcasing low toxicity in mammalian cells and an in vivo animal model (Caenorhabditis elegans). Conversely, compound 2 exhibited no activity. In silico predictions pointed to favorable oral bioavailability and the absence of PAINS similarities. Subsequently, a single oral dose of 400 mg/kg of compound 1 or praziquantel was administered to mice infected with adult (patent infection) or immature parasites (prepatent infection). Remarkably, in prepatent infections, 1 resulted in a significant reduction (approximately 50%) in both worm and egg burden, while praziquantel reduced worm and egg numbers by 30%. The superior efficacy of dehydrodieugenol B (1) compared to praziquantel in premature infections holds the potential to advance the development of new molecular prototypes for schistosomiasis treatment.

Design, synthesis, in silico studies and in vitro evaluation of isatin-pyridine oximes hybrids as novel acetylcholinesterase reactivators.

Organophosphorus poisoning caused by some pesticides and nerve agents is a life-threating condition that must be swiftly addressed to avoid casualties. Despite the availability of medical countermeasures, the clinically available compounds lack a broad spectrum, are not effective towards all organophosphorus toxins, and have poor pharmacokinetics properties to allow them crossing the blood-brain barrier, hampering cholinesterase reactivation at the central nervous system. In this work, we designed and synthesised novel isatin derivatives, linked to a pyridinium 4-oxime moiety by an alkyl chain with improved calculated properties, and tested their reactivation potency against paraoxon- and NEMP-inhibited acetylcholinesterase in comparison to the standard antidote pralidoxime. Our results showed that these compounds displayed comparable in vitro reactivation also pointed by the in silico studies, suggesting that they are promising compounds to tackle organophosphorus poisoning.