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• W2080380665 abstract "We have already established an in vitro culture system using murine macrophages infected with Leishmania donovani in which the time course of parasite growth is determined quantitatively. We adopted this system for the screening of three triazole-pyrimidine derivatives that would ideally prove to be effective against L. donovani with no toxicity to the host cell. Amphotericin B deoxycholate was used as the standard drug and gave a IC50 value of 3.89 microg/ml. The three triazole-pyrimidine compounds assayed have been reported to be potent growth inhibitors of L. donovani promastigote and amastigote stages. Compounds SPIV and SPVI exhibited the highest toxicity for extracellular forms of parasites, with IC50 values of 19.95 and 21.61 microg/ml, respectively. The triazole-pyrimidine SPV, although to a lower degree, also showed pronounced effects against promastigote forms with IC50 of 33.14 microg/ml. Drug activity was higher against amastigote than against promastigote stages. The compounds SPIV and SPVI interfered with the synthesis of macromolecules, affecting primarily DNA at the lower concentration tested (5 microg/ml), while SPV also showed interference, though to a lesser extent, and at a higher concentration (15 microg/ml) the percentage of inhibition rose considerably. The synthesis or RNA and proteins was also depressed significantly by these compounds at administration rates of 15 microg/ml. Ultrastructural alterations were evident in the main organelles of L. donovani (nucleus, kinetoplast, mitochondria), after the addition of the three compounds at a concentration of 5 microg/ml, to the in vitro culture. The in vitro promastigote forms of L. donovani can degrade glucose to carbon dioxide, and part of the carbon skeleton of the glucose is excreted as end metabolites. The excretion of these metabolites, mainly acetate, was also inhibited by the three compounds assayed, suggesting that this could be due to a direct effect on some of the enzymes related to this fermentation pathway or to the inhibition exerted by the compounds on enzyme synthesis." @default.
• W2080380665 created "2016-06-24" @default.
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• W2080380665 date "2004-12-03" @default.
• W2080380665 modified "2023-09-26" @default.
• W2080380665 title "Therapeutic Potential of New Pt(II) and Ru(III) Triazole-Pyrimidine Complexes against <i>Leishmania donovani</i>" @default.
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• W2080380665 doi "https://doi.org/10.1159/000081073" @default.
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