Current evidence suggests that endogenous dopamine may act as a neurotoxin following its oxidation to an oquinone
and reaction with cellular thiols, which are neutoxic, which may occur spontaneously or via reaction with tyrosinase
or some other enzymes. Tyrosinase (E.C. 126.96.36.199) with two cupper ions coordinated by three histidines is a bifunctional
enzyme that catalyses both the hydroxylation of tyrosine to L-DOPA and the consequent oxidation of the resulting
catechol-containing species to an o-quinone. Therefore, tyrosinase may play a role in neuromelanin formation in the
brain and could be central to dopamine neurotoxicity by contributing to the neurodegeneration associated with Parkinson’s
disease. In the present study, inhibitory effect of ascorbic acid against tyrosinase has been investigated and it has
shown a remarkable inhibitory effect in in vitro assays. Then, the in silico-based experiments established through molecular
docking calculations and scoring, docking search algorithm, and data plotting indicated that ascorbic acid is strong inhibitor
of tyrosinase by interacting with four amino acid units (histidine 263, serine 282, phenylalanine 264, and valin
283) in the active site of the enzyme. The compound also had two long distant hydrogen bindings with Cu1 and Cu2 with
distances of 3.57 and 3.41 A, respectively, through its O5 atom.
Ascorbic acid, in silico, in vitro, molecular docking, tyrosinase inhibition, vitamin C.
Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330 Ankara, Turkey.