Subscribe to RSS
Bioprospection of cytotoxic compounds in the Brazilian endemic tunicate Eudistoma vannamei
Eudistoma vannamei Millar, 1977 is an endemic tunicate from the northeastern coast of Brazil, widely distributed on the intertidal zones of the rocky beaches in Ceará State. Previously, its crude extract showed an interesting bioactivity profile. This work performed an in-depth chemical and pharmacological study of this extract. A highly bioactive alkaloid isolated from the polar ends of the dichloromethane fraction was identified in a cytotoxicity-guided fractionation protocol. Structure determination was accomplished by NMR, IR and MS/MS spectra analysis. Cytotoxicity was evaluated on 9 tumor cell lines (HL-60, K562, Molt-4, HCT-8, MDA MB 435, MDA MB 231, MX-1, SF 295 and B16) and one normal cell line (L929) and quantified by the MTT assay. Cell cycle was assessed by flow cytometry. IC50 was obtained in the ng-range (12–40ng/mL for most cell lines tested). Cell cycle studies indicate that the alkaloid induces a G2-M arrest (at 40ng/mL, 50%, 59% and 57% of cells were arrested at G2-M after 24, 48 and 72h treatment, respectively, against 22%, 25% and 17% for the non-treated culture). G2-M arrest effect is irreversible following drug removal and is initiated during the first 3h of treatment. Morphological analysis of treated cells stained with H/E suggests that arrest is actually occurring in G2 phase. Structure elucidation revealed this alkaloid to be a novel close analog to staurosporine.
Acknowledgements: FINEP, CNPq and InCB.