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Orenes Lorente, S. et al.

Biphenylquinuclidines as inhibitors of squalene synthase and growth of parasitic protozoa.

In this paper we describe the preparation of some biphenylquinuclidine derivatives and their evaluation as inhibitors of squalene synthase in order to explore their potential in the treatment of the parasitic diseases leishmaniasis and Chagas disease. The compounds were screened against recombinant Leishmania major squalene synthase and against Leishmania mexicana promastigotes, Leishmania donovani intracellular amastigotes and Trypanosoma cruzi intracellular amastigotes. Compounds that inhibited the enzyme, also reduced the levels of steroids and caused growth inhibition of L. mexicana promastigotes. However there was a lower correlation between inhibition of the enzyme and growth inhibition of the intracellular parasites, possibly due to delivery problems. Some compounds also showed growth inhibition of T. brucei rhodesiense trypomastigotes, although in this case alternative modes of action other than inhibition of SQS are probably involved.[1]

References

Biphenylquinuclidines as inhibitors of squalene synthase and growth of parasitic protozoa. Orenes Lorente, S., Gómez, R., Jiménez, C., Cammerer, S., Yardley, V., de Luca-Fradley, K., Croft, S.L., Ruiz Perez, L.M., Urbina, J., Gonzalez Pacanowska, D., Gilbert, I.H. Bioorg. Med. Chem. (2005) [Pubmed]

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