Naphthoquinones from Catalpa bungei “Jinsi” as potent antiproliferation agents inducing DNA damage

Structure-guided isolation of a CH 2 Cl 2 -soluble fraction of the heartwood of Catalpa bungei “Jinsi” provided two new naphthoquinones, 9-hydroxy-4-oxo- α -lapachone ( 1 ) and 6-hydroxy-4-oxo- α -lapachone ( 2 ), together with three undescribed ones ( 3 – 5 ) and six known ones ( 6 – 11 ). The structures were elucidated on the basis of spectroscopic methods including electronic circular dichroism calculation. The antiproliferative effects of these isolates were evaluated in human breast adenocarcinoma cells MCF7. (4 R )-4,9-dihydroxy- α -lapachone ( 5 ) and (4 S )-4,9-dihydroxy- α -lapachone ( 6 ) exhibited the significant activities with IC 50 values of 2.19 and 2.41 μM, respectively. The structure-activity relationship of 1 – 11 in the antiproliferative assay was then discussed. The most potent 5 and 6 were found to induce cell arrest in G1 phage through DNA damage. The findings provided some valuable insights for the discovery and structural modification of α -lapachone as antiproliferative lead compounds against human breast adenocarcinoma cells.