Data di Pubblicazione:
2018
Citazione:
Benzimidazole derivatives endowed with potent antileishmanial activity / T. Michele, E. Gabriele, P. Francesca, N. Basilico, S. Parapini, T. Bruno, L. Roberta, S. Fabio, A. Sparatore. - In: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. - ISSN 1475-6366. - 33:1(2018), pp. 210-226. [10.1080/14756366.2017.1410480]
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 IC50values 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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
2-benzyl-1-lupinylbenzimidazole derivatives; alkyl benzimidazolium salts; anti-leishmania agents; leishmania tropica and infantum; promastigotes; animals; antiprotozoal agents; benzimidazoles; cell line; cell survival; cercopithecus aethiops; dose-response relationship, drug; humans; Leishmania infantum; Leishmania tropica; molecular structure; parasitic sensitivity tests; structure-activity relationship; vero cells; pharmacology; drug discovery; pharmaceutical science
Elenco autori:
T. Michele, E. Gabriele, P. Francesca, N. Basilico, S. Parapini, T. Bruno, L. Roberta, S. Fabio, A. Sparatore
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