Jump to main content
Jump to site search

Issue 1, 2012
Previous Article Next Article

Amidines bearing benzofuroxan or benzimidazole 1,3-dioxide core scaffolds as Trypanosoma cruzi-inhibitors: structural basis for their interactions with cruzipain

Author affiliations

Abstract

Trypanosoma cruzi, the causative agent of Chagas' disease, affects tens of millions of South Americans. One of the most studied T. cruzi-biomolecules as a target for drug development is cruzipain, an essential cysteine proteinase of this parasite. Some of our recent studies identified amidine containing benzofuroxans as hit compounds for cruzipain inhibition with trypanosomicidal activities. Experimental and theoretical studies inspired us to modify these compounds by maintaining the amidine motif and using benzofuroxan and benzimidazole 1,3-dioxide systems as core scaffolds in order to obtain better cruzipain inhibitors. The new amidines had excellent trypanosomicidal activity, with good selectivity indexes, but without improved cruzipain-inhibitory activities compared with the parent compounds. The interaction of amidines with cruzipain has been investigated through a combined NMR -T1-differences, DOSY, and STD- and molecular docking approaches. Despite the low cruzipain-inhibition ability, our data suggest that these designed compounds have relevant structural features, i.e. aromatic groups and protonated moieties with stabilizing complex ability using stacking and electrostatic interactions, respectively, that bind reversibly to cruzipain.

Graphical abstract: Amidines bearing benzofuroxan or benzimidazole 1,3-dioxide core scaffolds as Trypanosoma cruzi-inhibitors: structural basis for their interactions with cruzipain

Back to tab navigation

Supplementary files

Publication details

The article was received on 31 Aug 2011, accepted on 30 Sep 2011 and first published on 04 Nov 2011


Article type: Concise Article
DOI: 10.1039/C1MD00223F
Citation: Med. Chem. Commun., 2012,3, 90-101

  •   Request permissions

    Amidines bearing benzofuroxan or benzimidazole 1,3-dioxide core scaffolds as Trypanosoma cruzi-inhibitors: structural basis for their interactions with cruzipain

    A. Merlino, D. Benitez, N. E. Campillo, J. A. Páez, L. W. Tinoco, M. González and H. Cerecetto, Med. Chem. Commun., 2012, 3, 90
    DOI: 10.1039/C1MD00223F

Search articles by author

Spotlight

Advertisements