In:
ChemMedChem, Wiley, Vol. 7, No. 1 ( 2012-01-02), p. 151-158
Abstract:
A series of inhibitors of plant enzymes of the non‐mevalonate pathway from herbicide research efforts at BASF were screened for antimalarial activity in a cell‐based assay. A 1,3‐diiminoisoindoline carbohydrazide was found to inhibit the growth of Plasmodium falciparum with an IC 50 value 〈 100 n M . Synthesis of a variety of derivatives allowed an improvement of the initial antimalarial activity down to IC 50 =18 n M for the most potent compound, the establishment of a structure–activity relationship, and the evaluation of the cytotoxic profile of the diiminoisoindolines. Furthermore, interesting configurational and conformational aspects for this class of compounds were studied by computational and X‐ray crystal structure analysis. Some of the compounds can act as tridentate ligands, forming 2:1 ligand–iron(III) complexes, which also display antimalarial activity in the nanomolar IC 50 range, paired with low cytotoxicity.
Type of Medium:
Online Resource
ISSN:
1860-7179
,
1860-7187
DOI:
10.1002/cmdc.201100441
Language:
English
Publisher:
Wiley
Publication Date:
2012
detail.hit.zdb_id:
2209649-8
SSG:
15,3