Activity of 2-acetylpyridine thiosemicarbazones against Trypanosoma rhodesiense in vitro

Abstract

Twenty-seven 2-acetylpyridine thiosemicarbazones and analogs were tested for antitrypanosomal activity against Trypanosoma rhodesiense using a semiautomated in vitro assay system. Activity was determined by relative inhibition of uptake of two radiolabeled macromolecular precursors, [methyl-3H]thymidine and L-[U-14C]leucine, as compared to untreated controls. It was observed that the nitrogen atom of the pyridyl moiety of the 2-acetylpyridine thiosemicarbazones was essential for antitrypanosomal activity. The 2-acetylpyridine thiosemicarbazones generally inhibited the uptake of L-[U-14C]leucine to a greater extent than they inhibited [methyl-3H]thymidine uptake. Twenty-four of the 27 compounds tested exhibited activity comparable to that found for the antitrypanosomal agent ethidium bromide.

Selective inhibition of herpes simplex virus ribonucleoside diphosphate reductase by derivatives of 2-acetylpyridine thiosemicarbazone

“…Screening of the compounds against other pathogenic organisms revealed that the compounds also possessed additional antiparasitic [3], antimicrobial [4,5], and antineoplastic [6] activity. We have since discovered that a number of these compounds are active against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) and that some of the derivatives inhibit the in vitro replication of the virus to a greater extent than they inhibit cellular DNA or protein synthesis [7], To date we have examined 111 derivatives and have found that certain compounds are active both in vitro and in a cutaneous herpes guinea pig model [8].…”

Activity of tunicamycin against Trypanosoma brucei in vitro and in vivo

“…This finding is consistent with those of Strickler and Patton (15) and Rovis and Dube (14) showing that TM inhibits normal glycosylation of the trypanosomal coat material. The results of our studies on incorporation of (2,4), the subsequent in vivo chemotherapeutic efficacy is presumed to be a result of enhanced immune response rather than a direct cytotoxic effect of TM on the parasite. A means of reducing host toxicity of TM without significantly decreasing its chemotherapeutic efficacy is presently being investigated in this laboratory.…”

Fine Structural Alterations in Trypanosoma rhodesiense Grown In Vitro, Treated with WR 1635771

“…Trypomastigotes of the Wellcome CT strain of T. rhodesiense were obtained from the blood of inoculated rats as previously described (1). A stock solution of WR 163577 dinitrate (Walter Reed Institute of Research drug inventory) was made by dissolving 25 mg drug in 1 ml dimethylsulfoxide (DMSO) and was diluted with parasite incubation medium (1) before use.…”

“…A stock solution of WR 163577 dinitrate (Walter Reed Institute of Research drug inventory) was made by dissolving 25 mg drug in 1 ml dimethylsulfoxide (DMSO) and was diluted with parasite incubation medium (1) before use. The antitrypanosomal activity of WR 163577 in vitro was quantitated by the inhibition of incorporation of radiolabeled thymidine and leucine into macromolecules of parasites exposed to 1-100 pg drug/ml, as described by Casero et al (1).…”