Cardamonin Presents in Vivo Activity against Schistosoma mansoni and Inhibits Potato Apyrase

Abstract

Schistosomiasis, a neglected tropical disease caused by Schistosoma species, harms over 250 million people in several countries. The treatment is achieved with only one drug, praziquantel. Cardamonin, a natural chalcone with in vitro schistosomicidal activity, has not been in vivo evaluated against Schistosoma. In this work, we evaluated the in vivo schistosomicidal activities of cardamonin against Schistosoma mansoni worms and conducted enzymatic apyrase inhibition assay, as well as molecular docking analysis of cardamonin against potato apyrase, S. mansoni NTPDase 1 and S. mansoni NTPDase 2. In a mouse model of schistosomiasis, the oral treatment with cardamonin (400 mg/kg) showed efficacy against S. mansoni, decreasing the total worm load in 46.8 % and reducing in 54.5 % the number of eggs in mice. Cardamonin achieved a significant inhibition of the apyrase activity and the three‐dimensional structure of the potato apyrase, obtained by homology modeling, showed that cardamonin may interact mainly through hydrogen bonds. Molecular docking studies corroborate with the action of cardamonin in binding and inhibiting both potato apyrase and S. mansoni NTPDases.

Recent Advances in Anti-Schistosomiasis Drug Discovery

“…Many natural products have demonstrated anti-schistosomiasis activity [10,[50][51][52]. The aurone scaffold is another source of antimalarial compounds [53,54] that has been investigated for anti-schistosomiasis potential [55,56].…”

“…The latter of those, perhexiline maleate (62), is an anti-angina drug whose efficacy against schistosomiasis had been studied previously [86,87]. Starting from those three hits, pharmacophore Leads resulting from a large high-throughput screening experiment (51)(52)(53)(54)(55)(56)(57)(58)(59).…”

“…Figure 9.Leads resulting from a large high-throughput screening experiment(51)(52)(53)(54)(55)(56)(57)(58)(59).…”

Identification of Asiaticoside from Centella erecta (Apiaceae) as Potential Apyrase Inhibitor by UF-UHPLC-MS and Its In Vivo Antischistosomal Activity

“…Additionally, previous studies have showed that the SmNTPDases isoforms have immune cross-reactivity with the potato ( Solanum tuberosum ) apyrase [ 9 , 10 , 11 ], sharing high homology and similarity in their active sites [ 9 , 10 , 11 , 12 ]. Regarding this, some natural compounds, such as cardamonin, have promoted the inhibition of both SmNTPDases and potato apyrase, also showing in vivo antischistosomal effects against S. mansoni [ 13 , 14 , 15 ]. Since its obtainment with high purity is easy, it has been proposed that potato apyrase may be used in the initial screening for selecting potential antischistosomal compounds with affinity for SmNTPDases in complex samples, such as plant extracts [ 13 , 15 ].…”

“…Regarding this, some natural compounds, such as cardamonin, have promoted the inhibition of both SmNTPDases and potato apyrase, also showing in vivo antischistosomal effects against S. mansoni [ 13 , 14 , 15 ]. Since its obtainment with high purity is easy, it has been proposed that potato apyrase may be used in the initial screening for selecting potential antischistosomal compounds with affinity for SmNTPDases in complex samples, such as plant extracts [ 13 , 15 ]. In this regard, in a preliminary assessment of some plant extracts against potato apyrase, the hydroalcoholic extract of Centella erecta (L.f.) Fern.…”