Core B continues to be responsible primarily for testing novel aromatic dicationic molecules, synthesized by Tidwell and Boykin for activity against P. carinii pneumonia (PCP) in the corticosteroid suppressed rat model of disease. New research to be performed by the core will include in vitro analysis of metabolic activation of prodrugs, synthesized by Tidwell and Boykin, prior to testing their anti-PCP activity in vivo. In addition, preliminary pharmacokinetic studies will be initiated for a limited number of selected compounds that exhibit excellent anti-PCP activity with minimal toxicity in the rat model (these advanced studies will be funded by the corporate sponsor, Pharm-Eco). Finally, this core will continue to supply organisms used in the biochemical and molecular studies by Dykstra.
| Patrick, D A; Hall, J E; Bender, B C et al. (1999) Synthesis and anti-Pneumocystis carinii pneumonia activity of novel dicationic dibenzothiophenes and orally active prodrugs. Eur J Med Chem 34:575-83 |
| Hall, J E; Kerrigan, J E; Ramachandran, K et al. (1998) Anti-Pneumocystis activities of aromatic diamidoxime prodrugs. Antimicrob Agents Chemother 42:666-74 |
| Tuttle, R H; Hall, J E; Tidwell, R R (1997) High-performance liquid chromatographic assay detects pentamidine metabolism by Fisher rat liver microsomes. J Chromatogr B Biomed Sci Appl 688:319-24 |
| Tidwell, R R; Jones, S K; Naiman, N A et al. (1993) Activity of cationically substituted bis-benzimidazoles against experimental Pneumocystis carinii pneumonia. Antimicrob Agents Chemother 37:1713-6 |
