Novel vanillin derivatives: Synthesis, anti-oxidant, DNA and cellular protection properties

Abstract

Antioxidants have been the subject of intense research interest mainly due to their beneficial properties associated with human health and wellbeing. Phenolic molecules, such as naturally occurring Resveratrol and Vanillin, are well known for their anti-oxidant properties, providing a starting point for the development of new antioxidants. Here we report, for the first time, the synthesis of a number of new vanillin through the reductive amination reaction between vanillin and a selection of amines. All the compounds synthesised, exhibited strong antioxidant properties in DPPH, FRAP and ORAC assays, with compounds 1b and 2c being the most active. The latter also demonstrated the ability to protect plasmid DNA from oxidative damage in the presence of the radical initiator AAPH. At cellular level, neuroblastoma SH-SY5Y cells were protected from oxidative damage (HO, 400 μM) with both 1b and 2c. The presence of a tertiary amino group, along with the number of vanillin moieties in the molecule contribute for the antioxidant activity. Furthermore, the delocalization of the electron pair of the nitrogen and the presence of an electron donating substituent to enhance the antioxidant properties of this new class of compounds. In our opinion, vanillin derivatives 1b and 2c described in this work can provide a viable platform for the development of antioxidant based therapeutics.

Synthesis of novel vanillin derivatives: novel multi-targeted scaffold ligands against Alzheimer's disease

“…It is worth mentioning that vanillin itself is more active than syringaldehyde in this assay (2.2 and 1.5 TE, respectively). 16 The imine 1 showed weaker scavenging activity compared to the amine 2 (2.1 and 3.9 TE, respectively) in this assay, confirming the role of the nitrogen's electron availability in the antioxidant activity.…”

“…The imine compound 1 showed no IC 50 up to concentration of 250 μM whereas its corresponding reduced amine showed an IC 50 of 50.7 μM, confirming our previous finding that an imine exhibits lower activity in free radical scavenging compared with the corresponding amine. 16 In addition, compound 3, bearing an extra methoxy group in the phenolic moiety compared to compound 2, turned out to betwo-fold more active (19.5 μM), confirming the important role of an extra methoxy group for the antioxidant activity. Interestingly, compound 4 showed similar activity to compound 3, although bearing only one methoxy group in its phenolic moiety (20.5 and 19.5 μM, respectively).…”

“…Compound 4 turned out to be the most active among the four vanillin derivatives (1.54 TE), confirming the role of the electronic delocalisation of the nitrogen electron in the antioxidant activity. 16 Again, tacrine on its own showed to be completely inactive in this assay at concentrations as high as 250 μM.…”

“…In addition, the latter compound protected the SH-SY5Y neuroblastoma cell line against hydrogen peroxide (400 μM) treatment, increasing the cell viability by 30% at compound concentrations as low as 10 μM. 16 Here we report the design and synthesis of four novel vanillin derivatives with multi-target functionalities that would be expected to exhibit antioxidant properties, as well as inhibitory AChE and amyloid Aβ aggregation activities ( Fig. 1).…”

“…It is worth noting that the protective effects of compound 4 are comparable to our previously reported compound 2c, which showed an increase in peroxide-treated cell viability by 26% at 5 μM, although 2c showed better antioxidant properties in both the DPPH, FRAP and ORAC assays. 16…”