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References and Notes
Table 4. Effect of non-nitrogen-containing bisphosphonates against
Trypanosoma brucei farnesyl pyrophosphate synthase activity for
compounds 4–8
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aValues are means of three experiments.
sites that clearly justify their effectiveness against T. cruzi
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1-Hydroxy-1,1-bisphosphonates were also able to block
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activity because it would provide an extra site of coor-
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acid as tetraethyl phosphonic ester voids its ability to
coordinate with Mg2+ resulting in a loss of efficacy both
to inhibit TcFPPS activity and to impair T. cruzi
growth. These results are very encouraging to improve
drug design because it would allow the use of homology
modelling of TcFPPS and TbFPPS taking into account
that the X-ray structure of the avian FPPS has been
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Work aimed at exploiting the potential biological activ-
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rigorous structure–activity relationship is currently
being pursued in our laboratory.
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Acknowledgements
31. Urbina, J. A.; Moreno, B.; Vierkotter, S.; Oldfield, E.;
Payares, G.; Sanoja, C.; Bailey, B. N.; Yan, W.; Scott, D. A.;
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32. Martin, M. B.; Sanders, J. M.; Kendrick, H.; de Luca-
Fradley, K.; Lewis, J. C.; Grimley, J. S.; Van Bussel, E. M.;
This work was supported by grants from Fundacion
Antorchas, the National Research Council of Argentina
(PIP 635/98), and the Universidad de Buenos Aires (X-
080) to J.B.R., and the Illinois Governor’s Venture
Technology Program to R.D.