Guanidine Alkaloids from Monanchora arbuscula: Chemistry and Antitumor Potential

Abstract

Five guanidine alkaloids, mirabilin B (1), 8bb-hydroxyptilocaulin (2), ptilocaulin (3), and a mixture of the 8b- and 8a-epimers, 4 and 5, of 8-hydroxymirabilin (1,8a;8b,3a-didehydro-8-hydroxyptilocaulin), were isolated from Monanchora arbuscula colonies collected off the northeastern Brazilian coast. All structures were elucidated by spectroscopic analysis, including 1D (1 H-, 13C- (BB), and 13C-DEPT) and 2D (COSY, HSQC, and HMBC) NMR experiments, and comparison with the literature data. The cytotoxicity of the isolated compounds were evaluated against four tumor cell lines, showing that mirabilin B (1) and the two epimers were inactive, while 8bb-hydroxyptilocaulin (2) and ptilocaulin (3) presented IC50 values in the range of 7.9 to 61.5 mm, and 5.8 to 40.0 mm, respectively. Further studies on the mechanism of action of ptilocaulin, using HL-60 leukemia cells, demonstrated that this guanidine compound induced apoptosis of the treated cells.