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WOS: 000518664600043 PubMed ID: 32075136 The chemical analysis of the sponge Dysidea avara afforded the known sesquiterpene quinone avarone, along with its reduced form avarol. To further explore the role of the thiazinoquinone scaffold as an antiplasmodial, antileishmanial and antischistosomal agent, we converted the quinone avarone into the thiazinoquinone derivative thiazoavarone. The semisynthetic compound, as well as the natural metabolites avarone and avarol, were pharmacologically investigated in order to assess their antiparasitic properties against sexual and asexual stages of Plasmodium falciparum, larval and adult developmental stages of Schistosomamansoni (eggs included), and also against promastigotes and amastigotes of Leishmania infantum and Leishmania tropica. Furthermore, in depth computational studies including density functional theory (DFT) calculations were performed. A toxic semiquinone radical species which can be produced starting both from quinone- and hydroquinone-based compounds could mediate the anti-parasitic effects of the tested compounds. Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR), PRIN Projects [2010C2LKKJ_006, 20154JRJPP_004]; Regione Campania-POR Campania FESR 2014/2020 "Combattere la resistenza tumorale: piattaforma integrata multidisciplinare per un approccio tecnologico innovativo alle oncoterapie-Campania Oncoterapie" [B61G18000470007]; CNR (National Research Council)-CNCCS (Collezione Nazionale di Composti Chimici e Centro di screening) "Rare, Neglected and Poverty Related Diseases -Schistodiscovery Project" [DSB.AD011.001.003] This research was supported by Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR), PRIN Projects 2010C2LKKJ_006; 20154JRJPP_004, by a grant from Regione Campania-POR Campania FESR 2014/2020 "Combattere la resistenza tumorale: piattaforma integrata multidisciplinare per un approccio tecnologico innovativo alle oncoterapie-Campania Oncoterapie" (Project N. B61G18000470007) and by the CNR (National Research Council)-CNCCS (Collezione Nazionale di Composti Chimici e Centro di screening) "Rare, Neglected and Poverty Related Diseases -Schistodiscovery Project" (DSB.AD011.001.003).

A deep study of the metabolic content of the tunicate Polycarpa aurata, collected from Indonesian coast, afforded the isolation of two novel alkaloids, polyaurines A (1) and B (2), along with two new p-substituted benzoyl derivatives (3 and 4) and four known compounds (5&ndash, 8). The structural elucidation of the new secondary metabolites was assigned by 1D, 2D NMR, and HRESIMS techniques. Computational studies resulted a useful tool to unambiguously determine in polyaurine B the presence of rarely found 1,2,4-thiadiazole ring. The effects of polyaurines A and B on mammalian cells growth and on the viability of different blood-dwelling Schistosoma mansoni (phylum: Platyhelminthes) stages, as well as egg production, were evaluated. Both compounds resulted not cytotoxic, interestingly some of the eggs produced by polyaurine A-treated adult pairs in vitro are smaller, deformed, and/or fragmented, therefore, polyaurine A could represent an interesting bioactive natural molecule to be further investigated.