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ABSTRACTIntroductionSchistosomiasis, one of the current Neglected Tropical Diseases (NTDs) affects over 230 million people globally, with nearly 700 million at risk in more than 74 countries. Praziquantel (PZQ) has served as the primary treatment for the past four decades; however, its effectiveness is limited as it solely eliminates adult worms. In regions where infections are frequent, PZQ exhibits only temporary efficacy and has restricted potential to disrupt the prolonged transmission of the disease.Areas coveredA comprehensive exploration using the PubMed database was conducted to review current pharmacotherapy approaches for schistosomiasis. This review also encompasses recent research findings related to potential novel therapeutics and the repurposing of existing drugs.Expert opinionCurrent schistosoma treatment strategies, primarily relying on PZQ, face challenges like temporary effectiveness and limited impact on disease transmission. Drug repurposing, due to economic constraints, is decisive for NTDs. Despite PZQ’s efficacy, its failure to prevent reinfection highlights the need for complementary strategies, especially in regions with persistent environmental foci. Integrating therapies against diverse schistosome stages boosts efficacy and impedes resistance. Uncovering novel agents is essential to address resistance concerns in tackling this neglected tropical disease. Integrated strategies present a comprehensive approach to navigate the complex challenges.

The synthesis of a new family of methoxy‐substituted [2.7]‐ and [2.8]paracyclophanes linked by 3‐oxapentamethylene‐1,5‐dioxy and hexamethylene‐1,6‐dioxy bridges has been carried out by using the McMurry methodology. Related indole compounds were also synthesised. Olefin‐to‐diol ratios depended on the bridge length, the structure of the aromatic ring and the reaction conditions. Macrocyclisation, the methoxy substituents and the presence of a rigid indole moiety restricted the conformational equilibria, as observed by NMR spectroscopy and according to theoretical calculations. The synthesised compounds display micromolar tubulin polymerisation inhibitory activity. The conformational implications on the tubulin polymerisation inhibitory activity derived from the macrocyclisation when compared with combretastatins, closely related stilbenes, are also discussed.

IminoDiels–Alder reactions between 1aryl or 1heteroaryl3trialkylsiloxy1,3butadienes and imines derived from ethyl glyoxylate have been studied. When an achiral imine was used, the diastereoselectivity depended on the nature of the aryl or heteroaryl system; diastereoselectivities > 90  were observed with methoxyphenyl or indolyl substituents, but were much lower for nitro substituents. High diastereoselectivities were also achieved if a chiral imine derived from methylbenzylamine was used as the dienophile. Solidsupported imine dienophiles yielded the Ndeprotected cycloadducts by direct cleavage from the resin with no diastereoselectivity. © WileyVCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008

A new family of diphenylethanes has been synthesized as conformationally restricted analogues of antimitotic combretastatins. The two phenyl rings are linked between the para‐phenolic positions through a 3‐oxapentamethylene or hexamethylene chain. The key macrocyclization step was achieved in moderate yields by using an intramolecular McMurry pinacol coupling of linked aromatic dialdehydes, except for the nitro‐substituted compounds. The relative stereochemistry of the isomeric pinacols was determined by a combination of spectroscopic, chemical derivatization, and molecular‐modeling approaches. The NMR spectra of these compounds (with a polyoxygenated crownophane skeleton) indicate severe conformational restrictions relative to their parent combretastatins; the rotation of the phenyl rings is hampered by interactions of their substituents and the linker and the conformational restrictions imposed by the substituted bridge.

A macrocyclic receptor based on a bischromenylurea and an ,‘-(o,o‘-dialkyl)diphenyl-p-xylylenediamine spacer provides a C2chiral cavity to associate carboxylates by H-bonds. The extent of the selectivity obtained for the racemic receptor 2and enantiomerically pure (S)-naproxen is 7.2:1. Steric repulsions close to the cavity are decisive for the chiral selectivity.