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 anti-tyrosinase activities. METHODS: Novel one-pot synthesis of Mannich base dopamine-connected vanillin (1a-l) derivatives can be achieved via green chemistry without using a catalyst. Newly-prepared compounds were characterised with FTIR and NMR ((1)H and (13)C) spectra, mass spectra, and elemental analyses. In total, 12 compounds (1a-l) were synthesised and their antioxidant and anti-tyrosinase activities evaluated. Antioxidant activities of 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), hydrogen peroxide (H(2)O(2)), and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and diammonium assays, ABTS(•+) radical scavenging, and linoleic acid peroxidation were used to screen all synthesised compounds (1a-l) for anti-tyrosinase activities and cytotoxicity against MCF-7 and Vero cell lines;. RESULTS: The compound 1k inhibited (IC(50):11.02µg/mL) the DPPH-scavenging activity to a greater extent than the standard BHT (IC(50):25.17µg/mL), and showed high activity in H(2)O(2) and NO scavenging assays. Compound 1e was more potent (96.21%) against ABTS and compound 1k was more potent (95.28%) against 2,2ʹ-azobis(2-amidinopropane)dihydrochloride antioxidant than the standard trolox. All synthesised compounds were screened for anti-tyrosinase inhibitory activity. Compound 1e had higher activity against tyrosinase (IC(50)=10.63 µg/mL), than kojic acid (IC(50)=21.52µg/mL), and was more cytotoxic (GI(50) 0.01µM) 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.