AUTHOR=Rauf Abdur , Uddin Ghias , Siddiqui Bina S. , Molnár Joseph , Csonka Ákos , Ahmad Bashir , Szabó Diana , Farooq Umar , Khan Ajmal 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=6

YEAR=2015

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2015.00293

DOI=10.3389/fphar.2015.00293

ISSN=1663-9812

ABSTRACT=<p>Three new dimeric naphthoquinones, 5,4′-dihydroxy-1′-methoxy-6,6′-dimethyl-7,3′-binaphthyl-1,4,5′,8′-tetraone (<bold>1</bold>), 5′,8′-dihydroxy-5-methoxy-6,6′-dimethyl-7,3′-binaphthyl-1,4,1′,4′-tetraone (<bold>2</bold>) and 8,5′,8′-trihydroxy-6,6′-dimethyl-7,3′-binaphthyl-1,4,1′,4′-tetraone (<bold>3</bold>), were isolated from the roots of <italic>Diospyros lotus.</italic> Their structures were elucidated by spectroscopic techniques, including 1D and 2D NMR, such as HSQC, HMBS, NOESY, and <italic>J</italic>-resolved. Compounds <bold>1–3</bold> were evaluated for their effects on the reversion of multidrug resistance (MDR) mediated by <italic>P</italic>-glycoprotein through use of the rhodamine-123 exclusion screening test on human <italic>ABCB1</italic> gene transfected L5178Y mouse T-cell lymphoma. Compounds <bold>1–3</bold> were also assessed for their antiproliferative and cytotoxic effects on L5178 and L5178Y mouse T-cell lymphoma lines. Both <bold>1</bold> and <bold>2</bold> 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.</p>