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

Abstract

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.

Synthesis of a New Series of Anthraquinone-Linked Cyclopentanone Derivatives: Investigating the Antioxidant, Antibacterial, Cytotoxic and Tyrosinase Inhibitory Activities of the Mushroom Tyrosinase Enzyme Using Molecular Docking

“…The test results of synthesized compounds were exactly opposite to those found for the inhibition of melanin formation. 42,43 The tyrosinase inhibitory activity of all synthesised compounds was evaluated using L-DOPA as the substrate by modifying a method previously reported by our research team, with slight modifications. This was done to evaluate their tyrosinase inhibitory activity.…”

Therapeutic aspects of biologically potent vanillin derivatives: A critical review

“…The obtained compounds were found to be better antioxidant potential with significant antityrosinase activity, determined by the ABTS, AAPH (2,2ʹazobis (2-amidinopropane) dihydrochloride) free-radical assay, Nitric oxide (NO) scavenging activity and H2O2 scavenging activity. Hence, both compounds were commonly bearing a dopamine-connected vanillin substituent in their structure and showed elevated antioxidant activity with a better IC50 (Half-maximal inhibitory concentration) value 43 . The structures of the above discussed compounds are given in figure 5.…”

Anticancer Activity of Mannich Bases: A Review of Recent Literature

“…Chirally pure β‐amino ketones 2 (Figure 1) obtained from isomeric norpseudoephedrines as amine reagents in the Mannich reaction exhibited moderate antiproliferative activity against A549 and HepG‐2 cells [10] . Starting from dopamine as amine reagent and vanillin as aldehyde component, a series of ketonic Mannich bases 3 (Figure 1) have been prepared, and their evaluation as cytotoxic agents against MCF‐7 cell line afforded a few highly active compounds, the most potent of them being Mannich base 3 (R=4‐BrC 6 H 4 , IC 50 =0.02 μM) [11] . Eight Mannich bases 4 of acrylophenones (Figure 1) have been tested against four tumor cell lines (Ca9‐22 human gingival carcinoma, HSC‐2 human oral squamous carcinoma, HSC‐3 human oral squamous carcinoma and HSC‐4 human oral squamous carcinoma) and three non‐tumor cell lines, and the analogue with Ar=4‐CH 3 C 6 H 4 has been identified as the most active compound in this series (cytotoxic concentrations CC 50 between 3 and 7 μM) [12] .…”

“…[10] Starting from dopamine as amine reagent and vanillin as aldehyde component, a series of ketonic Mannich bases 3 (Figure 1) have been prepared, and their evaluation as cytotoxic agents against MCF-7 cell line afforded a few highly active compounds, the most potent of them being Mannich base 3 (R = 4-BrC 6 H 4 , IC 50 = 0.02 μM). [11] Eight Mannich bases 4 of acrylophenones (Figure 1) have been tested against four tumor cell lines (Ca9-22 human gingival carcinoma, HSC-2 human oral squamous carcinoma, HSC-3 human oral squamous carcinoma and HSC-4 human oral squamous carcinoma) and three non-tumor cell lines, and the analogue with Ar = 4-CH 3 C 6 H 4 has been identified as the most active compound in this series (cytotoxic concentrations CC 50 between 3 and 7 μM). [12] Potential cytotoxic ketonic Mannich bases that are derived from cycloalkanones as substrates, aromatic aldehydes as aldehyde component, and have arylamino moieties in their structure can be illustrated by aminobenzyl derivatives 5 of cyclohexanone (Figure 1), whose activity against HCT-116 and MDA-MB-231 cell lines was poor, [13] or by aminobenzylated cyclododecanones 6 (Figure 1), the most potent candidate in the series with a broad activity against PANC-1, ACHN, HCT-116, H460, CALU-1 and MCF-7 cell lines being 6 (Ar 1 = 2-F 3 CC 6 H 4 ; Ar 2 = C 6 H 5 ; IC 50 ranging from 0.2 to 0.5 μM).…”