Serum Albumin Binding Studies with Gold(III) Anticancer Compounds
Author:
Pauline OlsenMentor:
Jack Eichler, Assistant Professor of Pedagogy, University of California RiversideGold(III) complexes bearing polypyridyl ligands based on the 1,10-phenanthroline (phen) and 2,2’-bipyrydine (bipy) structural architectures have shown promising anti-cancinogenic effects in a variety of tumor cell lines. In particular, our laboratory has found that a five-coordinate gold(III) complex possessing 2,9-di-sec-butyl-1,10-phenanthroline, [(sec-butylphen)AuCl3], was found to possess promising anticancer activity against in vitro tumor cell lines, but limited activity against in vivo tumors in mice. The current working hypothesis proposes that the limited in vivo activity of [(sec-butylphen)AuCl3] is due to the fact this neutral complex may be binding to the blood protein serum albumin, which subsequently impedes its delivery to the tumor. The research reported here describes initial experiments designed to determine if the [(sec-butylphen)AuCl3] complex has significant interaction with serum albumin, and if structural analogues of this gold(III) complex possessing more polar substituent might have decreased serum albumin binding. In order to test if decreasing non-polarity functionality could possibly change the serum albumin binding, a 2-mono-sec-butylphen gold complex, [(mono-sec-butylphen)AuCl3], was synthesized. Serum albumin binding studies with [(sec-butylphen)AuCl3] and [(mono-sec-butylphen)AuCl3] have been completed, and initial data indicate that both complexes interact with this protein in these non-biological experimental conditions. Additionally, in order to test if polarity will conceivable alter the effect of serum albumin binding, the molecule 2,9-di-phenyl-4-methylphen, [(phenyl-methylphen)AuCl3], has been synthesized. Syntheses aimed at adding polar functional groups to the phen backbone are currently underway, and albumin binding studies on these new complexes will be subsequently carried out.