Design, synthesis, and evaluation of an activity-based probe for cellular imaging of monoamine oxidases

Abstract

Monoamine oxidase, a FAD-containing enzyme, is responsible for the degradation of various neurotransmitters and xenobiotic amines to aldehydes. The selective targeting of monoamine oxidases (MAOs) may also help to visualize the development of related diseases. A new activity-based fluorescent probe containing acetamide group has been synthesized. To minimize the interactions with the dye, a hexyl linker was inserted between MAO tracer 2-(alkylamino)-acetamide and fluorescein. Enzyme inhibitory activities of probe 1, compounds 2 and 3 were assayed to confirm a high binding affinity of the probe to MAOs (IC50 value: 35.1 μM for MAO-A and 150.8 μM for MAO-B). Cell imaging was investigated in breast cancer cell MCF-7 with confocal laser scanning microscopy, and the results showed that this new acetamide-based MAO probe has a high affinity and specificity toward MAO, and thus it is a promising candidate for sensitive MAO detection in living system.