Zn(ii)-based tyramine-conjugated porphyrin complex as an active tyrosinase inhibitor for potential neuroprotection by improving the mitochondrial homeostasis

Abstract

Neurodegenerative diseases are related to dopamine oxidation and mitochondrial dysfunction. Polyphenol-conjugated compounds for mitochondrial targeting can be employed as multifunctional candidates against neurodegeneration. Herein, a polyphenol compound, P4TA, was designed and developed via the conjugation of porphyrin (P) with four tyramine (TA) tethers. Complex ZnP4TA was obtained by the coordination of Zn(II) with P4TA. A series of spectroscopic experiments were performed and the results demonstrate that both P4TA and ZnP4TA can bind with TYR, inhibiting the oxidation of tyrosine by tyrosinase (TYR). Furthermore, the rotenone (RO)-induced oxidation of tyrosine by TYR in SH-SY5Y cells can be sufficiently attenuated by both P4TA and ZnP4TA. The mitochondrial membrane potential of SH-SY5Y cells was assessed by JC-1 staining in vitro, confirming that ZnP4TA could enhance mitochondrial function and restore mitochondrial homeostasis, thereby exerting neuroprotective effects. TYR activity assays further validated the role of ZnP4TA as a potent TYR inhibitor. These findings suggest that ZnP4TA holds great potential as a multifunctional agent for neuroprotection by simultaneously modulating TYR activity and mitochondrial homeostasis.