Madurastatins with Imidazolidinone Rings: Natural Products or Side-Reaction Products from Extraction Solvents?

Madurastatins are a group of pentapeptides containing an oxazoline moiety, and, in a few cases, an imidazolidinone ring as an additional structural feature. In our search for new potential antiparasitic metabolites from natural sources, we studied the acetone extracts from a culture of sp. CA-135719.

Oxa, Thia, Heterocycle, and Carborane Analogues of SQ109: Bacterial and Protozoal Cell Growth Inhibitors.

We synthesized a library of 48 analogs of the cell growth inhibitor SQ109 in which the ethylene diamine 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 N-geranyl group by another hydrophobic species. Compounds were tested against (H37Rv and/or Erdman), , , , , and two human cell lines (human embryonic kidney, HEK293T, and the hepatocellular carcinoma, HepG2). Most potent activity was found against , the causative agent of human African trypanosomiasis, and involved targeting of the mitochondrial membrane potential with 15 SQ109 analogs being more active than was SQ109 in cell growth inhibition, having IC values as low as 12 nM (5.