The applicant plans to synthesize and spectroscopically characterize novel symmetric organorhenium(I) and organotechnetium(I) lipophilic cationic complexes targeted to the MDR1 P-glycoprotein, specifically exploring the effects of: a) combining aromatic ring halogenation with ether functionalities, and b) alkyl spacers positioned between the substituted aryl and isonitrilic moieties; to explore an alternative chemical pathway for synthesis of a closely related class of novel mixed ligand rhenium(III) isonitrile-metal complexes to enhance the chances for success in producing bioactive Re-complexes; use his MDR bioassays to screen and characterize novel metal-isonitrile complexes for modulation of P-glycoprotein transport function; and, to perform preclinical validation of in vivo of promising lead metal-isonitrile modulators.
| Rao, V V; Dahlheimer, J L; Bardgett, M E et al. (1999) Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood-cerebrospinal-fluid drug-permeability barrier. Proc Natl Acad Sci U S A 96:3900-5 |
| Rao, V V; Herman, L W; Kronauge, J F et al. (1998) A novel areneisonitrile Tc complex inhibits the transport activity of MDR P-glycoprotein. Nucl Med Biol 25:225-32 |
| Goldberg, D E; Sharma, V; Oksman, A et al. (1997) Probing the chloroquine resistance locus of Plasmodium falciparum with a novel class of multidentate metal(III) coordination complexes. J Biol Chem 272:6567-72 |
