Cytotoxic and Schistosomidal Activities of Extract, Fractions and Isolated Compounds from Zanthoxylum Leprieurii (Rutaceae)

Ernestine Nkwengoua Tchouboun Zondegoumb, Whistler Lucain Dibahteu Tankoua, Emmanuel Mouafo Tekwu, Olivier Eteme Ndogo, Rodrigo Santos A. de Araujo, Giovanni Vidari, Yan Liu, Shihong Luo, Shenghong Li, Francisco Jaime Bezerra Mendonça Junior, Luciana Scotti, Marcus Tullius Scotti, Maria do Carmo Alves de Lima, Barthelemy Nyasse

Abstract


Schistosomiasis is a major and chronic neglected tropical disease. The existing treatment does not kill immature schistosomes and have serious adverse side effect.  It is well known that some parasites are responsible for causing specific cancers in humans including bladder cancer from Schistosoma haematobium infection. So, novel drugs discovery is an urgent need. In this study, were evaluated in vitro the cytotoxic on human hepatocarcinoma (HepG2) and normal cells (Chang liver), and the schistosomicidal properties of crude extract, fractions and isolated compounds (1-Hydroxy-3-methoxy-N-methylacridone (1) described in this species from Cameroon for the first time, Scoparone (2), and Arborinine (3)) from powdered fruits of Zanthoxylum leprieurii (Rutaceae). All fractions: hexanic (FH), methylene chloride (FC), ethyl acetate (FA) and methanolic (FM) killed all the cercariae within 2 hours exposure and presents LC50 values between 2 and 3 μg/ml; Compounds 1 and 3 also displayed a good in vitro schistosomicidal activity against cercariae with LC50 values of 78.78 and 6.98 μg/mL, respectively. For antitumor activity compounds 1-3 and fraction FC presents good activity with IC50 values range 18.27 - 74.61 μg/mL on HepG2 cells, however most of these were more toxic on Chang cells than to HepG2 cells, with only exception for compound 2. The acridone Arborinine (3) can constitute a good lead for the research of schistosomiasis alternative therapy, and the coumarin Scoparone (2) can be used in drug design as scaffold for design new potential anticancer agents.


Keywords


Acridone Alkaloids; Arborinine; Scoparone; Cercariae; Cytotoxic activity, Schistosomicidal activity; Zanthoxylum leprieurii.

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References


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