Benzimidazole derivatives endowed with potent antileishmanial activity. (1st January 2018)

• Record Type: Journal Article
• Authors: Tonelli, Michele; Gabriele, Elena; Piazza, Francesca; Basilico, Nicoletta; Parapini, Silvia; Tasso, Bruno; Loddo, Roberta; Sparatore, Fabio; Sparatore, Anna
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 33:Number 1(2018)
• Page Start: 210
• Page End: 226
• Publication Date: 2018-01-01
• Subjects: Leishmania tropica and infantum -- promastigotes -- anti-leishmania agents -- alkyl benzimidazolium salts -- 2-benzyl-1-lupinylbenzimidazole derivatives; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2017.1410480
• Languages: English
• ISSNs: 1475-6366

Abstract

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 IC50 values in the low micromolar/sub-micromolar range. Among the set of 2-(long chain)alkyl benzimidazoles, whose heterocyclic head was quaternised, compound8 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, compound28 (2-(4-chlorobenzyl)-1-lupinyl-5-trifluoromethylbenzimidazole) was 12-/7-fold more potent than miltefosine, but exhibited a further improved SI. Therefore, compounds8 and28 represent interesting hit compounds, susceptible of structural modification to improve their safety profiles. Graphical Abstract: