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 (¹H and ¹³C) 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 (H₂O₂), 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 (IC₅₀:11.02μg/mL) the DPPH-scavenging activity to a greater extent than the standard BHT (IC₅₀:25.17μg/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 2,2ʹ-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 (IC₅₀=10.63 μg/mL), than kojic acid (IC₅₀=21.52μg/mL), and was more cytotoxic (GI₅₀ 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.

Keywords: Mannich base, grindstone chemistry, antioxidant, anti-tyrosinase activity, cytotoxicity


中文翻译：

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通过磨石法合成多巴胺介导的香兰素多组分衍生物：抗氧化、抗酪氨酸酶和细胞毒活性的应用

目的：本研究旨在通过在香草醛中添加多巴胺来确定多巴胺对抗氧化和抗酪氨酸酶活性的贡献程度。本研究实现了通过涉及绿色化学方法的一步反应制备多巴胺相关香草醛曼尼希碱衍生物的合成，并研究了抗氧化和抗酪氨酸酶活性。
方法：可以通过绿色化学在不使用催化剂的情况下实现新型一锅法合成曼尼希碱多巴胺连接的香草醛 ( 1a-l ) 衍生物。^{用 FTIR 和 NMR（ 1} H 和¹³ C）光谱、质谱和元素分析对新制备的化合物进行了表征。总共有 12 种化合物（1a-l) 被合成并评估了它们的抗氧化和抗酪氨酸酶活性。2,2-diphenyl-1-picrylhydrazyl (DPPH)、一氧化氮 (NO)、过氧化氢 (H ₂ O ₂ ) 和 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) 的抗氧化活性(ABTS) 和二铵测定、ABTS ^•+自由基清除和亚油酸过氧化用于筛选所有合成化合物 ( 1a-l ) 的抗酪氨酸酶活性和对 MCF-7 和 Vero 细胞系的细胞毒性；。
结果：化合物1k抑制(IC ₅₀ :11.02μg/mL)DPPH清除活性比标准BHT(IC ₅₀:25.17μg/mL)，并在 H ₂ O ₂和 NO 清除测定中显示出高活性。化合物1e对 ABTS 的效力更强（96.21%），化合物1k对 2,2′-偶氮二（2-脒基丙烷）二盐酸盐抗氧化剂的效力比标准 trolox 更强（95.28%）。筛选所有合成的化合物的抗酪氨酸酶抑制活性。化合物1e对酪氨酸酶的活性（IC ₅₀ =10.63 μg/mL）高于曲酸（IC ₅₀ =21.52μg/mL），对MCF-7细胞系的细胞毒性（GI ₅₀ 0.01μM）高于阿霉素标准品和其他测试的化合物。
结论：在这项研究中，发现所有化合物都具有显着的抗氧化和抗酪氨酸酶活性。与其他化合物相比，化合物1e和1k在所有测定中均表现良好。此外，这项研究成功地鉴定了几种具有抗氧化和抗酪氨酸酶活性的有前景的分子。

关键词：曼尼希碱，磨石化学，抗氧化，抗酪氨酸酶活性，细胞毒性