title: Synthesis and biological evaluation of platinum-acridine hybrid agents modified with bipyridine non-leaving groups.
abstract: The use of 2,2'-bipyridines (4,4'-R(2)-2,2'-bpy; R=H, Me, OMe, CF(3)) as non-leaving groups (L-L) in platinum-acridinylthiourea conjugates, [PtCl(L-L)(ACRAMTU)](NO(3))(2), has been investigated. All bpy-substituted complexes (2-5) show micromolar activity in HL-60 (leukemia) and H460 (lung) cancer cell lines but proved to be significantly less potent than the prototypical compound (1) containing aliphatic ethane-1,2-diamine. NMR and mass spectrometry data indicate that bpy accelerates the reaction of platinum with DNA nitrogen, but the resulting adducts are more labile than those formed by the prototype.
authors.affiliation: Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Kheradi
authors.forename: Gilda
authors.initials: G
authors.lastname: Saluta
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Kucera
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Day
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bierbach
mesh_terms: D015082:2,2'-Dipyridyl / Q000138:chemical synthesis / Q000737:chemistry*; D000166:Acridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D006801:Humans; D017671:Platinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; D017671:Platinum Compounds; D015082:2,2'-Dipyridyl