Synthesis and biological evaluation of platinum-acridine hybrid agents modified with bipyridine non-leaving groups.
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.
Kheradi
Alexander R
AR
Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA.
Saluta
Gilda
G
Kucera
Gregory L
GL
Day
Cynthia S
CS
Bierbach
Ulrich
U
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
D000166:Acridines; D000970:Antineoplastic Agents; D017671:Platinum Compounds; D015082:2,2'-Dipyridyl