A Rare Class of New Dimeric Naphthoquinones from Diospyros lotus have Multidrug Reversal and Antiproliferative Effects

Three new dimeric naphthoquinones, 5,4'-dihydroxy-1'-methoxy-6,6'-dimethyl-7,3'-binaphthyl-1,4,5',8'-tetraone (1), 5',8'-dihydroxy-5-methoxy-6,6'-dimethyl-7,3'-binaphthyl-1,4,1',4'-tetraone (2) and 8,5',8'-trihydroxy-6,6'-dimethyl-7,3'-binaphthyl-1,4,1',4'-tetraone (3), were isolated from the roots of Diospyros lotus. Their structures were elucidated by spectroscopic techniques, including 1D and 2D NMR, such as HSQC, HMBS, NOESY, and J-resolved. Compounds 1-3 were evaluated for their effects on the reversion of multidrug resistance (MDR) mediated by P-glycoprotein through use of the rhodamine-123 exclusion screening test on human ABCB1 gene transfected L5178Y mouse T-cell lymphoma. Compounds 1-3 were also assessed for their antiproliferative and cytotoxic effects on L5178 and L5178Y mouse T-cell lymphoma lines. Both 1 and 2 exhibited promising antiproliferative and MDR-reversing effects in a dose-dependent manner. The effects of the tested compounds on the activity of doxorubicin were observed to vary from slight antagonism to antagonism.