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Warifteine and milonine, alkaloids isolated from Cissampelos sympodialis Eichl: cytotoxicity on rat hepatocyte culture and in V79 cells

2003; Elsevier BV; Volume: 142; Issue: 1-2 Linguagem: Inglês

10.1016/s0378-4274(03)00064-x

1879-3169

Patrícia S. Melo, Horacinna Maria de Medeiros Cavalcante, José Maria Barbosa‐Filho, Margareth de Fátima Formiga Melo Diniz, Isac Almeida de Medeiros, Marcela Haun,

Alkaloids: synthesis and pharmacology

Two alkaloids were isolated from the leaves of Cissampelos sympodialis; a bisbenzylisoquinoline compound named warifteine and a novel 8,14-dihydromorphinandienone alkaloid named milonine. The cytotoxic effects of these alkaloids were assayed in cultured hepatocytes and V79 fibroblasts. Three independent endpoint assays for cytotoxicity in vitro were used: the nucleic acid content (NAC), tetrazolium reduction (MTT) and neutral red uptake (NRU). Milonine was less toxic than warifteine in both cell cultures. The IC50 values determined in the three different viability assays were around 100 and 400 μM after milonine treatment of V79 cells or hepatocytes. IC50 values ranging from 10 to 35 μM were obtained for warifteine in the viability tests evaluated in V79 cells and hepatocytes. Due to the similar cytotoxic effects detected on V79 cells and hepatocytes, probably warifteine and milonine induced toxic effects independent to the cytochrome P450. This hypothesis was corroborated by the results where Cimetidine (1.0 mM), a traditional cytochrome P450 inhibitor, did not protect the cells from the toxic action of warifteine or milonine. In conclusion, these alkaloids merit further investigations as potential novel pharmacological agents although milonine was less toxic than warifteine in the cells models investigated.