Solution aggregation of anti-trypanosomal N-(2-naphthylmethyl)ated polyamines

• Published in: Journal of photochemistry and photobiology. A, Chemistry. Chemistry., 2004-03, Vol.162 (2), p.387-398
• Main Authors: Pandey, Siddharth, Fletcher, Kristin A, Baker, Sheila N, Baker, Gary A, DeLuca, Joseph, Fennie, Michael F, O’Sullivan, Mary C
• Format: Article
• Language: English
• Subjects: Excimer; Exciplex; Fluorescence; Naphthyl; Polyamines; Spermidine; Spermine
• ISSN: 1010-6030; 1873-2666
• DOI: 10.1016/S1010-6030(03)00380-0

Trypanosomatidae parasites are responsible for many human and animal diseases including African sleeping sickness, Chagas’ disease, and Nagana cattle disease. Since current treatment of trypanosome infections is difficult and often ineffective in controlling the chronic phases of these diseases, more effective anti-trypanosomal drugs are urgently needed. One class of polyamines containing hydrophobic side chains shows promise. However, conformational information regarding their interaction with the target enzyme trypanothione reductase has yet to be obtained. As prelude to such studies, we have made preliminary studies of novel spermine and spermidine analogs bearing one or two N-substituted 2-naphthylmethyl groups dissolved in aqueous solution. Our studies suggest the pH-dependent formation of fluorescent aggregates involving either the encounter of two excited-state naphthyl groups (“excimer”) or formation of an excited-state complex (“exciplex”) formed as a consequence of amine-to-naphthyl electron transfer. These spectral changes may be used to explore the mechanism by which N-(2-naphthylmethyl) polyamine analogs exert their toxic effects toward the design of improved candidates for anti-trypanosomal chemotherapy.