Abstract

In the past two years pneumocystis pneumonia has become the major opportunistic disease in patients with acquired immunodeficiency syndrome (AIDS). The disease is rapidly progressive with a mortality rate over 40% despite treatment, whereas the mortality rate approaches 100% in untreated cases. Pentamidine is an effective chemotherapeutic agent but is highly toxic. Various combinations and analogs of pyrimethamine and sulfadiazine have been used with varying degrees of success. However, AIDS patients with pneumocystis pneumonia have not responded well to such treatment. The objective of this contract is to identify new drugs which have potential for use in the treatment of pneumocystis pneumonia in AIDS patients, utilizing animal models and/or in vitro techniques. Evaluation of such promising drugs in AIDS patients will then be carried out under a separate project.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research and Development Contracts (N01)
Project #
N01AI072648-004
Application #
3596116
Study Section
Project Start
1987-07-10
Project End
1992-07-09
Budget Start
1989-03-30
Budget End
1990-07-09
Support Year
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

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
Berger, B J; Naiman, N A; Hall, J E et al. (1992) Primary and secondary metabolism of pentamidine by rats. Antimicrob Agents Chemother 36:1825-31
Blagburn, B L; Sundermann, C A; Lindsay, D S et al. (1991) Inhibition of Cryptosporidium parvum in neonatal Hsd:(ICR)BR Swiss miceby polyether ionophores and aromatic amidines. Antimicrob Agents Chemother 35:1520-3
Berger, B J; Reddy, V V; Le, S T et al. (1991) Hydroxylation of pentamidine by rat liver microsomes. J Pharmacol Exp Ther 256:883-9
Dykstra, C C; Tidwell, R R (1991) Inhibition of topoisomerases from Pneumocystis carinii by aromatic dicationic molecules. J Protozool 38:78S-81S
Bartlett, M S; Queener, S F; Tidwell, R R et al. (1991) 8-Aminoquinolines from Walter Reed Army Institute for Research for treatment and prophylaxis of Pneumocystis pneumonia in rat models. Antimicrob Agents Chemother 35:277-82
Jones, S K; Hall, J E; Allen, M A et al. (1990) Novel pentamidine analogs in the treatment of experimental Pneumocystis carinii pneumonia. Antimicrob Agents Chemother 34:1026-30
Bell, C A; Hall, J E; Kyle, D E et al. (1990) Structure-activity relationships of analogs of pentamidine against Plasmodium falciparum and Leishmania mexicana amazonensis. Antimicrob Agents Chemother 34:1381-6