Novel Lipophilic Acetohydroxamic Acid Derivatives Based on Conformationally Constrained Spiro Carbocyclic 2,6-Diketopiperazine Scaffolds with Potent Trypanocidal Activity

Citations Over TimeTop 11% of 2011 papers

Abstract

We describe novel acetohydroxamic acid derivatives with potent activity against cultured bloodstream-form Trypanosoma brucei and selectivity indices of >1000. These analogues were derived from conformationally constrained, lipophilic, spiro carbocyclic 2,6-diketopiperazine (2,6-DKP) scaffolds by attaching acetohydroxamic acid moieties to the imidic nitrogen. Optimal activity was achieved by placing benzyl groups adjacent to the basic nitrogen of the 2,6-DKP core. S-Enantiomer 7d was the most active derivative against T. brucei (IC(50) = 6.8 nM) and T. cruzi (IC(50) = 0.21 μM).

Related Papers

• → Discovery of Potent N-Ethylurea Pyrazole Derivatives as Dual Inhibitors of Trypanosoma brucei and Trypanosoma cruzi(2019)22 cited
• → Inhibition of urease activity but not growth of Helicobacter pylori by acetohydroxamic acid.(1991)17 cited
• → Influence of acetohydroxamic acid on some activities in vitro of the rumen microbiota(1968)17 cited
• → Synthesis of a bicyclic oxamazin. A novel heteroatom activated β-lactam(1996)18 cited
• → Protein synthesis in the rumen: Ruminal urease inhibition by acetohydroxamic acid(1969)