BIOCHEM.SCREENS FOR AGENTS EFF. AGAINST AIDS-RELATED OIS

Project: Research project

Project Details

Description

This contract supports the National Institute of Allergy and Infectious
Diseases (NIAID) in its mission to stimulate the discovery of improved
therapies of AIDS-associated opportunistic infections. While a few drugs
are available to treat some of these infections, more efficacious and less
toxic therapies are needed. Additionally, accepted therapies do not exist
for certain opportunistic infections (OIs). In vitro assays and biochemical prescreening have been used effectively to
identify structure-activity relationships (SAR) of potential new
therapies. Biochemically based screening tests may be particularly useful
in discovery of anti-OI drugs because: l) certain AIDS-related
opportunistic pathogens cannot be cultured in vitro, 2) such assays are
rapid, and more efficient for pathogens that replicate poorly in vitro, 3)
enzymes critical in the replication of certain pathogens have been
identified and may be exploitable therapeutically, 4) analogous host
enzymes may be identified that could be used to simultaneously evaluate
selectivity, and 5) development of high volume assays permits detailed SAR
evaluations of compounds. Such a biochemical prescreening project has been
operational at NIAID since 1988 and several promising compounds have been
identified. Specifically, compounds were rationally selected from an
automated data base and evaluated for inhibition of enzymes of folic acid
metabolism isolated from Pneumocystis carinii, Toxoplasma gondii and host
mammalian tissues. The purpose of this contract is to continue efforts to screen agents in
enzymatic assays of metabolic pathways essential to the replication of
AIDS-related opportunistic pathogens. Pathogens to be addressed include
P. carinii, T.gondii. and Mycobacterium avium.
StatusFinished
Effective start/end date8/15/938/14/96

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $288,166.00
  • National Institutes of Health: $271,609.00

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)

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