title: A Rare Class of New Dimeric Naphthoquinones from Diospyros lotus have Multidrug Reversal and Antiproliferative Effects.
abstract: 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.
authors.affiliation: Department of Geology, University of Swabi Swabi, Pakistan.
authors.forename: Abdur
authors.initials: A
authors.lastname: Rauf
authors.affiliation: Institute of Chemical Sciences, University of Peshawar Peshawar, Pakistan.
authors.forename: Ghias
authors.initials: G
authors.lastname: Uddin
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi Karachi, Pakistan.
authors.forename: Bina S
authors.initials: BS
authors.lastname: Siddiqui
authors.affiliation: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged Szeged, Hungary.
authors.forename: Joseph
authors.initials: J
authors.lastname: Molnár
authors.affiliation: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged Szeged, Hungary.
authors.forename: Ákos
authors.initials: Á
authors.lastname: Csonka
authors.affiliation: Center of Biotechnology and Microbiology, University of Peshawar Peshawar, Pakistan.
authors.forename: Bashir
authors.initials: B
authors.lastname: Ahmad
authors.affiliation: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged Szeged, Hungary.
authors.forename: Diana
authors.initials: D
authors.lastname: Szabó
authors.affiliation: Department of Chemistry, COMSATS Institute of Information Technology Abbottabad, Pakistan.
authors.forename: Umar
authors.initials: U
authors.lastname: Farooq
authors.affiliation: Department of Chemistry, COMSATS Institute of Information Technology Abbottabad, Pakistan.
authors.forename: Ajmal
authors.initials: A
authors.lastname: Khan
keywords: Diospyros lotus; MDR; P-glycoprotein; antiproliferative; human ABCB1 gene transfected mouse T-cell lymphoma; naphthoquinones