The objective of this project is to identify folate analogs and analogs of p-aminobenzoic acid (PABA) with greater therapeutic potential for the treatment of opportunistic infections in patients with AIDS than the current clinically used agents. To accomplish this objective folate analogs will be screened for inhibitory activity against dihydrofolate reductase (DHFR) isolated form two protozoans (Pneumocystis carinii and Toxoplasma gondii) and from mammalian rat liver. Also, analogs of PABA will be tested for inhibition of dihydropteroate synthetase (DHPS) isolated from the two protozoans. Uptake into intact cells of selected potent inhibitors of the DHFRs, differential inhibitors of the protozoal DHFR and potent inhibitors of DHPS will be evaluated. Protection of intact cells from selected potent, non-differential, inhibitors of DHFR also may be evaluated.
