Journal of Enzyme Inhibition and Medicinal Chemistry 2009-10-01

Design, synthesis and evaluation of 3-(imidazol- 1-ylmethyl)indoles as antileishmanial agents. Part II.

Francis Giraud, Cedric Loge, Fabrice Pagniez, Damien Crepin, Sophie Barres, Carine Picot, Patrice Le Pape, Marc Le Borgne

Index: J. Enzyme Inhib. Med. Chem. 24(5) , 1067-75, (2009)

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Abstract

A new series of 1-benzyl-3-(imidazol-1-ylmethyl)indoles were synthesized according to a previous 3D-QSAR predictive model and assayed for their antiparasitic activity upon Leishmania mexicana promastigotes. The biological results obtained for these twelve molecules showed an IC(50) ranging from 2.3 to 32 microM and mainly illustrated the importance of the hydrophobic parameter the para-position of the benzyl group. In order to improve the activities of these compounds and to check the potential influence of the electronic parameter on this particular position, a Craig diagram was used to select original electro-donating and lipophilic substituents. Synthesis and biological evaluation of ten new compounds (IC(50) between 2.5 and 5.4 microM) confirmed that only the hydrophobic field is essential for a high level of activity.