1 research outputs found
Oxa, Thia, Heterocycle, and Carborane Analogues of SQ109: Bacterial and Protozoal Cell Growth Inhibitors
We
synthesized a library of 48 analogues of the Mycobacterium
tuberculosis cell growth inhibitor SQ109 in which
the ethylenediamine linker was replaced by oxa, thia, or heterocyclic
species, and in some cases, the adamantyl group was replaced by a
1,2-carborane or the <i>N</i>-geranyl group by another hydrophobic
species. Compounds were tested against <i>M. tuberculosis</i> (H37Rv and/or Erdman), Mycobacterium smegmatis, Bacillus subtilis, Escherichia coli, Saccharomyces cerevisiae, Trypanosoma brucei, and two human
cell lines (human embryonic kidney, HEK293T, and the hepatocellular
carcinoma, HepG2). The most potent activity was found against <i>T. brucei</i>, the causative agent of human African trypanosomiasis,
and involved targeting of the mitochondrial membrane potential with
15 SQ109 analogues being more active than was SQ109 in cell growth
inhibition, having IC<sub>50</sub> values as low as 12 nM (5.5 ng/mL)
and a selectivity index of ∼300