New Trypanosoma brucei acting derivatives incorporating 1-(4-phenyl)adamantane and 1-(4-phenoxyphenyl)adamantane

TL;DR

Researchers designed new adamantane-based compounds that show strong activity against Trypanosoma brucei, a parasite causing African sleeping sickness.

Contribution

The study introduces novel adamantane derivatives with enhanced trypanocidal activity and selectivity through strategic molecular modifications.

Findings

Aromatic imidazolines and linear amidines showed notable activity against T. brucei.

Compound 4c exhibited a promising EC50 of 0.16 μM and an SI of 17.

Functionalization with aminoguanylhydrazone and thiosemicarbazone moieties improved compound efficacy.

Abstract

In this work, we describe the design, synthesis and evaluation of novel functionalised 1-(4-phenyl)adamantane and 1-(4-phenoxyphenyl)adamantane derivatives. Based on previous findings, we incorporated a phenyl ring between the adamantane core and the pharmacophoric side chain to enhance the activity and selectivity index (SI). The aromatic imidazolines 1a–d and the linear amidines 2a,b and 3a,b exhibited notable activity against T. brucei. The 1-(4-phenyl)adamantane 1-(4-phenoxyphenyl)adamantane core was further functionalized with the aminoguanylhydrazone and thiosemicarbazone moieties. 2-[(E)-4-(1-adamantyl)benzylidene]hydrazine-1-carbothioamide 4c emerged as a promising trypanocidal agent with an EC50 of 0.16 μM and an SI of 17. Future studies will focus on optimizing the length and the distance of the side chain between the aromatic ring and the chromophores to further enhance the activity and selectivity of these molecules.

New 1-(4-phenyl)adamantane and 1-(4-phenoxyphenyl)adamantane derivatives, functionalised with imidazolines, linear amidines, aminoguanylhydrazone and thiosemicarbazone moieties present activity against T. brucei.

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