Tunable regulatory activities of 1,10-phenanthroline derivatives towards acid sphingomyelinase and Zn(ii)-amyloid-β

We report a new series of small molecules able to achieve the tunability of modulatory activities against acid sphingomyelinase (ASM) and Zn(ii)-bound amyloid-β [Zn(ii)-Aβ], two pathological targets found in the brain affected by Alzheimer's disease. Rational tuning of the hydrophobicity and Zn(ii) binding affinity of the 1,10-phenanthroline (phen) framework successfully yielded compounds as chemical modulators for ASM (4 and 5), Zn(ii)-Aβ (phen, 1, and 2), or both (3).