Dopamine-Mediated Vanillin Multicomponent Derivative Synthesis via Grindstone Method: Application of Antioxidant, Anti-Tyrosinase, and Cytotoxic Activities

Purpose: This study aimed to determine the extent of contribution of dopamine to antioxidant and anti-tyrosinase activities, by dopamine addition to vanillin. This study achieved the synthesis of dopamine-associated vanillin Mannich base derivatives prepared via a one-step reaction involving a green chemistry approach, and investigation of antioxidant and antityrosinase activities. Methods: Novel one-pot synthesis of Mannich base dopamine-connected vanillin (1a-1) derivatives can be achieved via green chemistry without using a catalyst. Newly-prepared compounds were characterised with FTIR and NMR (H-1 and C-13) spectra, mass spectra, and elemental analyses. In total, 12 compounds (la-1) were synthesised and their antioxidant and anti-tyrosinase activities evaluated. Antioxidant activities of 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), hydrogen peroxide (H2O2), and 2,2'-azino-bis(3-ethylbenzothia-zoline-6-sulfonic acid) (ABTS), and diammonium assays, ABTS radical scavenging, and linoleic acid peroxidation were used to screen all synthesised compounds (la-1) for antityrosinase activities and cytotoxicity against MCF-7 and Vero cell lines;. Results: The compound 1k inhibited (IC50 :11.02 mu g/mL) the DPPH-scavenging activity to a greater extent than the standard BHT (IC50:25.17 mu g/mL), and showed high activity in H2O2 and NO scavenging assays. Compound 1e was more potent (96.21%) against ABTS and compound 1k was more potent (95.28%) against 2,2'-azobis(2-amidinopropane)dihydrochloride antioxidant than the standard trolox. All synthesised compounds were screened for anti-tyrosinase inhibitory activity. Compound le had higher activity against tyrosinase (IC50=10.63 mu g/mL), than kojic acid (IC50 =21.52 mu g/mL), and was more cytotoxic (GI(50) 0.01 mu M) against MCF-7 cell line than the doxorubicin standard and other tested compounds. Conclusion: In this study, all compounds were found to possess significant antioxidant and anti-tyrosinase activities. Compounds 1e and 1k performed well, compared with other compounds, in all assays. In addition, this study successfully identified several promising molecules that exhibited antioxidant and anti-tyrosinase activities.

Automated summary

This study successfully synthesized dopamine-associated vanillin Mannich base derivatives using a green chemistry approach, and evaluated their antioxidant and anti-tyrosinase activities. Compound 1e and 1k showed promising results in both antioxidant and anti-tyrosinase assays, indicating their potential as effective molecules in these activities.