Synthesis and evaluation of nitroheterocyclic aromatic adamantane amides with trypanocidal activity. Part II

Abstract

In this article, we report the design, synthesis, and biological evaluation of a new series of nitroheterocyclic aromatic adamantane amides targeting trypanosomes. These compounds feature diverse substituents on the adamantane scaffold, variations in side chain linker length, and a range of nitroheterocyclic moieties. This work represents a continuation of our previous efforts, with a particular focus on elucidating the structural and functional role of the linker connecting the phenyladamantane core to the nitroheterocyclic ring. The structure–activity relationship data underscore the importance of strategic modifications in enhancing the pharmacological profile of these compounds against trypanosome parasites. Further modifications are recommended to optimize the physicochemical properties of the current derivatives to improve intracellular targeting of trypanosomatids, an important clinical stage in their life cycle.