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The toxic profile of lawsone (2-hydroxy-[1,4]naphthoquinone) and a series of [1,4]naphthoquinone derivatives was evaluated against the brine shrimp Artemia salina and against the mollusk Biomphalaria glabrata, the main transmitting vector of schistosomiasis in Brazil. Of the seventeen compounds tested nine fell below the threshold of 100 µg/mL set for potential molluscicidal activity by the World Health Organization. As a general rule derivatives with non-polar substituents presented the highest molluscicidal activities. These substances showed significant toxicity in A. salina lethality bioassay.

The chalcone-like series 1a-1g was efficiently synthesized from Morita-Baylis-Hillman reaction (52-74% yields). Compounds 1a-1g were designed by molecular hybridization based on the anti-inflammatory drug methyl salicylate (3) and the antileishmanial moiety of the Morita-Baylis-Hillman adducts 2a-2g. The 1a-1g compounds were much more actives than precursor series 2a-2g, for example, IC(50)=7.65 μM on Leishmania amazonensis and 10.14 μM on Leishmania chagasi (compound 1c) when compared to IC(50)=50.08 μM on L. amazonensis and 82.29 μM on L. chagasi (compound 2c). The IC(50) values of compound 3 (228.49 μM on L. amazonensis and 261.45 μM on L. chagasi) and acryloyl salicylate 4 (108.50 μM on L. amazonensis and 118.83 μM on L. chagasi) were determined here, by the first time, on Leishmania.

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