Synthesis and Evaluation of Nifurtimox–Adamantane Adducts with Trypanocidal Activity

다국어 초록 (Multilingual Abstract)

The synthesis and pharmacological evaluation of C1‐substituted adamantane hydrazones, their C2‐substituted isomers, and C1‐substituted adamantane furanoic carboxamides is described. These new adamantane derivatives exhibited an interesting pharmacological profile in terms of trypanocidal activity and selectivity. The most active adduct with the best selectivity in this study was found to be the phenylacetoxy hydrazone 1 b (2‐[4‐(tricyclo[3.3.1.13,7]dec‐1‐yl)phenyl]‐N′‐[(5‐nitrofuran‐2‐yl)methylene]acetohydrazide; EC50=11±0.9 nm, SITb=770).
Adamant against trypanosomes! This study involves the search for new drugs against vector‐borne kinetoplastid diseases. We inserted a phenyl ring between the adamantane core and the hydrazone side chain of new nifurtimox–adamantane adducts, and the resulting compounds were found to have higher trypanocidal activity and lower toxicity than the parent drug. The most active adduct with the best selectivity in this study was found to be the phenylacetoxy hydrazone 1 b (EC50=11±0.9 nm, SITb=770).