Benzimidazole Derivatives Endowed with Potent Antileishmanial Activity

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2017 Dec 14

PMID 29233048

Citations 15

Authors

Michele Tonelli

Elena Gabriele

Francesca Piazza

Nicoletta Basilico

Silvia Parapini

Bruno Tasso

Roberta Loddo

Fabio Sparatore

Anna Sparatore

Affiliations

Soon will be listed here.

Abstract

Two sets of benzimidazole derivatives were synthesised and tested in vitro for activity against promastigotes of Leishmania tropica and L. infantum. Most of the tested compounds resulted active against both Leishmania species, with IC values in the low micromolar/sub-micromolar range. Among the set of 2-(long chain)alkyl benzimidazoles, whose heterocyclic head was quaternised, compound 8 resulted about 100-/200-fold more potent than miltefosine, even if the selectivity index (SI) versus HMEC-1 cells was only moderately improved. In the set of 2-benzyl and 2-phenyl benzimidazoles, bearing a basic side chain in position 1, compound 28 (2-(4-chlorobenzyl)-1-lupinyl-5-trifluoromethylbenzimidazole) was 12-/7-fold more potent than miltefosine, but exhibited a further improved SI. Therefore, compounds 8 and 28 represent interesting hit compounds, susceptible of structural modification to improve their safety profiles.

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