title: Bifendate-chalcone hybrids: a new class of potential dual inhibitors of P-glycoprotein and breast cancer resistance protein.
abstract: We previously described bifendate-chalcone hybrids as potent P-glycoprotein inhibitors. In the present work, we determine whether these compounds could reverse breast cancer resistance protein (BCRP, ABCG2)-mediated multidrug resistance using HEK293/BCRP cells which was BCRP-transfected stable HEK293 cells. Results indicated that compounds 8d, 8f, 8g and 8h could significantly enhance mitoxantrone accumulation in HEK293/BCRP cells via inhibiting BCRP drug efflux function. The most active compound 8g exhibited little intrinsic cytotoxicity (IC₅₀>100 μM), and could reverse BCRP-mediated drug resistance independent of decreasing BCRP expression level. Notably, 8g had little inhibitory effect on multidrug resistance-associated protein 1 (MRP1, ABCC1), another drug efflux transporter. The present findings, together with the previous results, suggest that 8g might be act as dual inhibitors of P-gp and BCRP.
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, Xuzhou 221004, People's Republic of China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Environmental Pharmacy, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, People's Republic of China.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Department of Environmental Pharmacy, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, People's Republic of China. Electronic address: p_h2002@hotmail.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Sixun
authors.initials: S
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People's Republic of China. Electronic address: zyhtgd@hotmail.com.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000737:chemistry*; D002599:Chalcone / Q000008:administration & dosage* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D057809:HEK293 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D001713:Biphenyl Compounds; D009363:Neoplasm Proteins; C465548:bifendate; D002599:Chalcone
keywords: Alkoxyl biphenyl; BCRP inhibitor; Bifendate-chalcone hybrids; Multidrug resistance