title: Biological activity of hydantoin derivatives on P-glycoprotein (ABCB1) of mouse lymphoma cells.
abstract: BACKGROUND
  Hydantoin derivatives possess a variety of biochemical and pharmacological properties. Although hydantoin compounds are studied extensively, there are not many studies that investigate their anticancer properties.
  
  
  METHODS
  Thirty hydantoin compounds were evaluated for their efflux modulating effects in cancer cells using a rhodamine 123 accumulation assay and real-time fluorometry based on the intracellular accumulation of ethidium bromide.
  
  
  RESULTS
  The 30 derivatives were screened by real-time fluorometry for rhodamine 123 accumulation. Among the selected derivatives, compounds SZ-7, LL-9, BS-1, MN-3, P3, RW-15b, AD-26, RW-13, AD-29 and KF-2 significantly increased the retention of rhodamine 123. Compounds AD-26, AD-29, RW-13, KF-2, BS-1, MN-3, RW-15b and JH-63 showed synergistic effect with doxorubicin on mouse lymphoma cells. Furthermore, compound SZ-7 had indifferent effect with doxorubicin.
  
  
  CONCLUSIONS
  These results indicated the role of chemical modifications within the hydantoin ring for its potential inhibition of the ABCB1 transporter. The most active structures contained aromatic substituents as well as some tertiary amine fragments.
authors.affiliation: Unit of Mycobacteriology and 2Unidade de Parasitologia e Microbiologia Medicas,Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa Lisboa, Portugal.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Spengler
authors.forename: Miguel
authors.initials: M
authors.lastname: Evaristo
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Handzlik
authors.forename: Julianna
authors.initials: J
authors.lastname: Serly
authors.forename: Joseph
authors.initials: J
authors.lastname: Molnár
authors.forename: Miguel
authors.initials: M
authors.lastname: Viveiros
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kiéc-Kononowicz
authors.forename: Leonard
authors.initials: L
authors.lastname: Amaral
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D004996:Ethidium / Q000493:pharmacokinetics; D005470:Fluorometry; D006801:Humans; D006827:Hydantoins / Q000494:pharmacology*; D007940:Leukemia L5178 / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020112:Rhodamine 123 / Q000493:pharmacokinetics; D014162:Transfection
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D006827:Hydantoins; D020112:Rhodamine 123; D004317:Doxorubicin; C507084:Abcb1b protein, mouse; D004996:Ethidium