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

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 IC₅₀ ranging from 2.3 to 32 μM 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 (IC₅₀ between 2.5 and 5.4 μM) confirmed that only the hydrophobic field is essential for a high level of activity.

Keywords::

• QSAR
• craig diagram
• 3-(imidazol-1-ylmethyl)indoles
• leishmania mexicana
• antileishmanial agents

Acknowledgement

Declaration of interest: The authors report no conflicts of interest.