Design and computational evaluation of <i>E</i>-stilbene-bearing 1,3,4-oxadiazole derivatives as potential tyrosinase inhibitors using DFT, molecular docking and ADMET studies.
The study found that E-stilbene-based 1,3,4-oxadiazole derivatives have promising inhibitory effects on tyrosinase, with the most active compounds showing IC50 values of 0.32 ± 0.03 µM and 0.76 ± 0.01 µM.
Where it sits
this study against the rest of the tesofensine corpusSummary and findings
A series of E-stilbene-bearing 1,3,4-oxadiazole derivatives were synthesized and evaluated for their inhibitory effects on tyrosinase. The compounds exhibited IC50 values ranging from 0.32 ± 0.03 µM to 6.28 ± 0.05 µM. Compounds 5d and 5b showed the most significant activity with IC50 values of 0.32 ± 0.03 µM and 0.76 ± 0.01 µM, respectively.
Abstract
A series of <i>E</i>-stilbene-bearing 1,3,4-oxadiazole derivatives (4a-b and 5a-f) was synthesized <i>via</i> the Mizoroki-Heck reaction and evaluated as inhibitors of tyrosinase, a vital enzyme involved in melanin biosynthesis. The synthesized compounds were structurally confirmed through NMR spectroscopy (<sup>1</sup>H NMR, <sup>13</sup>C NMR), infrared spectroscopy (FT-IR), and mass spectrometry. Nearly all derivatives exhibited inhibitory effects against tyrosinase with IC<sub>50</sub> values ranging from 0.32 ± 0.03 µM to 6.28 ± 0.05 µM. Among them, compounds 5d and 5b illustrated the most significant inhibitory activity, with IC<sub>50</sub> values of 0.32 ± 0.03 µM and 0.76 ± 0.01 µM, respectively. Molecular docking against tyrosinase (PDB: 2Y9X) revealed strong binding affinities (-10.0 kcal mol<sup>-1</sup> and -8.5 kcal mol<sup>-1</sup>) exceeding those of the standard inhibitors kojic acid and ascorbic acid. Molecular dynamics simulation (100 ns), DFT analysis, and ADMET predictions further supported the stability, reactivity, and favorable pharmacokinetic behavior of the active compounds. These findings indicate that <i>E</i>-stilbene-based 1,3,4-oxadiazole derivatives hold significant potential as promising scaffolds for the development of new tyrosinase inhibitors for potential dermatological and cosmetic applications.