allopurinol-riboside and 9-deazainosine

We have developed a simple and reproducible system for infecting a human macrophage cell line (U937) with stationary-phase Leishmania donovani promastigotes. Four days after infection, greater than 90% of the promastigotes had transformed to amastigotes. The antileishmanial agents allopurinol riboside, formycin B, 9-deazainosine, and sodium stibogluconate effectively inhibited the growth of L. donovani amastigotes in this cell line. To study the capability of amastigotes in the U937 cell line to carry out biochemical reactions that could be monitored experimentally, we incubated the cells with radiolabeled 9-deazainosine. This purine analogue underwent metabolism in the amastigote phase similar to that occurring in the promastigote phase. This cell line should be useful for studies of parasite maturation and differentiation, parasite-human interactions, and antiparasitic drugs.

Topics: Allopurinol; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Cell Line; Formycins; Humans; Inosine; Leishmania donovani; Macrophages; Ribonucleosides

Three analogs of inosine, formycin B, allopurinol ribonucleoside, and 9-deazainosine, were tested for their ability to suppress proliferation of Pneumocystis carinii in culture with WI-38 cells. The organism was inhibited by 9-deazainosine at 10 micrograms/ml, and there was some inhibition at 1 microgram/ml. Formycin B was effective only at 40 micrograms/ml. Allopurinol ribonucleoside had little effect.

Topics: Allopurinol; Animals; Antiprotozoal Agents; Cells, Cultured; Drug Combinations; Formycins; Inosine; Microbial Sensitivity Tests; Pneumocystis; Rats; Ribonucleosides; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination