Faculty of Pharmacy, Department of Pharmaceutical Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG, 36036-900, Brazil.
Programa de Pós-graduação em Modelagem Computacional, Departamento de Ciência da Computação, ICE, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, 36036-900, Brazil.
Chem Biodivers. 2021 Nov;18(11):e2100604. doi: 10.1002/cbdv.202100604. Epub 2021 Oct 27.
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.
血吸虫病是一种由血吸虫属引起的被忽视的热带病，在多个国家危害着超过 2.5 亿人。目前，仅有吡喹酮一种药物可用于治疗。卡达明是一种具有抗血吸虫活性的天然查尔酮，但尚未在体内对血吸虫进行评估。在这项工作中，我们评估了卡达明对曼氏血吸虫成虫的体内杀血吸虫活性，并进行了酶氨酸酶抑制试验，以及卡达明对马铃薯氨酸酶、曼氏血吸虫 NTPDase-1 和曼氏血吸虫 NTPDase-2 的分子对接分析。在血吸虫病的小鼠模型中，卡达明（400mg/kg）的口服治疗对曼氏血吸虫有效，使总虫负荷减少了 46.8%，并使小鼠体内的卵数减少了 54.5%。卡达明对氨酸酶活性有显著的抑制作用，通过同源建模获得的马铃薯氨酸酶的三维结构表明，卡达明可能主要通过氢键相互作用。分子对接研究证实了卡达明与马铃薯氨酸酶和曼氏血吸虫 NTPDases 结合并抑制其活性的作用。
