Thiourea-Based H2S-Releasing Pramipexole Hybrids as Neuroprotective Agents.
AI interpretation is pending for this paper.
What the AI sees
Not AI summarized yet.
Research significance
Pending deeper interpretation.
Source abstract
Multitarget hybrid molecules are a promising strategy for treating complex neurodegenerative disorders such as Parkinson's disease (PD), where dopaminergic dysfunction, oxidative stress, neuroinflammation, and cellular senescence coexist and drive disease progression. Here, we developed pramipexole-derived hydrogen sulfide (H2S)-releasing hybrids using, for the first time, a thiourea moiety as an H2S-donating linker to extend the therapeutic profile of pramipexole beyond dopamine receptor agonism. The hybrids were synthesized and characterized, and their H2S-releasing properties were assessed by amperometric and intracellular detection assays. Among the series, compound 2e (PRAM-ADA) showed the most efficient and sustained H2S release, indicating a favorable thiol-dependent release profile. PRAM-ADA was further evaluated for antioxidant and anti-senescent activities in BV2 microglial cells, as well as for chemical and enzymatic stability under simulated physiological conditions. The hybrid significantly reduced LPS-induced reactive oxygen species accumulation and attenuated oxidative stress-induced cellular senescence, demonstrating a superior cytoprotective profile compared with pramipexole. These findings support the concept that combining dopaminergic activity with controlled H2S donation enhances antioxidant and anti-senescent responses, indicating their potential as multitarget agents with neuroprotective properties relevant to neurodegenerative disorders, including PD.