New hydrazones of 5-nitro-2-furaldehyde with adamantanealkanohydrazides: synthesis and in vitro trypanocidal activity??

MedChemComm Pub Date: 2016-05-11 DOI: 10.1039/C6MD00035E

Abstract

Nifurtimox, a hydrazone of 5-nitro-2-furaldehyde is used therapeutically against Trypanosoma brucei and Trypanosoma cruzi infections. Exploiting our previous observation that adamantane derivatives display trypanocidal activity, we designed and synthesised a range of hydrazones of 5-nitro-2-furaldehyde with adamantane alkanohydrazides. The most promising compounds had >20 times greater activity (IC50 ～ 100 nM) than nifurtimox, with selectivity indices of 20–80. SAR studies revealed that activity is associated with increased lipophilicity and influenced by conformational flexibility. Derivatives lacking a nitro group were practically inactive against both parasites. The approaches described demonstrate the feasibility of enhancing the potency of chemical entities with known trypanocidal activity.

Graphical abstract: New hydrazones of 5-nitro-2-furaldehyde with adamantanealkanohydrazides: synthesis and in vitro trypanocidal activity
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