Asymmetrical diaromatic guanidinium/2-aminoimidazolinium derivatives: synthesis and DNA affinity.
In this paper we report the synthesis of three families of new amidine-based aromatic derivatives as potential DNA minor groove binding agents for the treatment of cancer. The preparation of monoguanidine, mono-2-aminoimidazoline, and asymmetric diphenylguanidine/2-aminoimidazoline derivatives (compounds 1a-c to 8a-c) is presented. The affinity of these substrates and of a family of mono- and bis-isoureas (previously prepared in Rozas' laboratory) for DNA was evaluated by means of DNA thermal denaturation measurements. In particular, compounds 2c, 5c, 6c, 7c, and 8c were found to bind strongly both to natural DNA and to adenine-thymine oligonucleotides, showing a preference for the adenine-thymine base pair sequences.
Nagle
Padraic S
PS
School of Chemistry, University of Dublin, Trinity College, Dublin 2, Ireland.
Rodriguez
Fernando
F
Kahvedzić
Amila
A
Quinn
Susan J
SJ
Rozas
Isabel
I
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D001482:Base Composition; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D019791:Guanidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D009691:Nucleic Acid Denaturation / Q000187:drug effects; D011061:Poly A / Q000737:chemistry / Q000378:metabolism; D044366:Transition Temperature
D000970:Antineoplastic Agents; D007093:Imidazoles; D011061:Poly A; C015465:poly(dA); C014973:2-aminoimidazole; D004247:DNA; D019791:Guanidine