title: Semiautomated assessment of in vitro activity of potential antileishmanial drugs.
abstract: We have compared the in vitro activity of six agents against macrophage-contained Leishmania tropica amastigotes determined by the conventional Giemsa staining procedure, with the activity determined by the semiautomated assessment of incorporation of radiolabeled uracil into the nucleic acid of the organisms. Although the mean 50% effective dose of Pentostam by Giemsa staining (4.1 micrograms/ml) was somewhat higher than that by uracil incorporation (2.8 micrograms/ml), the ED50S for the other two clinical agents (pentamidine, 0.035 versus 0.037 micrograms/ml; amphotericin B, 0.67 versus 0.70 micrograms/ml) and for three promising experimental agents (ketoconazole, 11.3 versus 11.3 micrograms/ml; the 8-aminoquinoline WR 6026, 1.6 versus 1.5 micrograms/ml formycin B, 0.018 versus 0.017 micrograms/ml) were virtually identical. The radiolabeling technique has several advantages over the Giemsa staining procedure. These include the need for relatively few macrophages, rapid and objective data generation, and viability of the test organism being measured. The successful application of the radiolabeling technique to at least six different chemical classes of compounds suggests that it would be useful for the routine assessment of antileishmanial activity in vitro.
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D000666:Amphotericin B / Q000494:pharmacology; D000967:Antimony Sodium Gluconate / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D001331:Automation; D001399:Azure Stains; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005573:Formycins / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007654:Ketoconazole / Q000494:pharmacology; D007895:Leishmania tropica / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000469:parasitology*; D010419:Pentamidine / Q000494:pharmacology; D014316:Tritium; D014498:Uracil / Q000378:metabolism
chemical_list: D000634:Aminoquinolines; D000981:Antiprotozoal Agents; D001399:Azure Stains; D005573:Formycins; D014316:Tritium; C034561:formycin B; D014498:Uracil; D010419:Pentamidine; D000666:Amphotericin B; D007654:Ketoconazole; C080436:8-aminoquinoline; D000967:Antimony Sodium Gluconate