title: The interaction of 4-thiazolidinone derivatives containing indolin-2-one moiety with P-glycoprotein studied using K562 cell lines.
abstract: P-glycoprotein (P-gp) is an active drug efflux pump, which exists widely in various MDR tumor cells, conferring drug resistance to tumor cells during chemotherapy. Some 4-thiazolidinone derivatives containing indolin-2-one moiety are novel anti-tumor compounds. The aim of this study was to evaluate the transport activity of P-gp towards 4-thiazolidinone derivatives containing indolin-2-one moiety (as mixtures of 2Z, 5Z and 2E, 5Z isomers) and the transport inhibition activities of the derivatives to P-gp, the results of which could provide crucial information for the further separation of and development on the derivatives with excellent anti-tumor activities. The results indicate that the further separation and development should be focused on compounds 7, 10, 12 and 13 (tumor cell cytotoxic P-gp modulators) and compounds 8, 9, 17 and 18 (non-substrates of P-gp), which exhibit anti-tumor activities and could overcome P-gp mediated MDR. Furthermore, the results of molecular docking indicate that Ser222, a residue in TM4 domain of P-gp, exhibits an intriguing feature in that it interacts with all of the derivatives related with P-gp transport in a significant way, including both typical substrates and modulators of P-gp. Meanwhile, the compounds showing no interaction with Ser222 are mainly from the category of non-substrates of P-gp. Therefore, the interaction between Ser222 and the tested derivative would provide useful information for the further development on 4-thiazolidinone derivatives containing indolin-2-one moiety.
authors.affiliation: Department of Interventional Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116021, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radiology, Hubei Cancer Hospital, 116 Zhuodaoquan Southern Road, Hongshan District, Wuhan, 430079, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tao
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
authors.affiliation: Department of Parasitology, College of Basic Medical Sciences, Dalian Medical University, 9 South Lvshun Road Western Section, Dalian 116044, Liaoning, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Bao
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: yanfangzhao@126.com.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Parasitology, College of Basic Medical Sciences, Dalian Medical University, 9 South Lvshun Road Western Section, Dalian 116044, Liaoning, China. Electronic address: wangyulin1971@126.com.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Wang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D020014:K562 Cells; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D053778:Thiazolidines / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D007211:Indoles; D053778:Thiazolidines; C456900:indolin-2-one
keywords: 4-Thiazolidinone derivatives; Cytotoxicity assay; Molecular docking; P-glycoprotein