Walatimine (Vanillyl butyl imine): A New Ketimine from Schiff base Synthesis and Evaluation of its Antioxidant, Antibacterial and Antifungal Properties

Abstract

Background of study:  Vanillin is a white crystalline compound which is a phenolic aldehyde with a balsamic flavour. It is widely obtained from vanilla bean-pods amongst very many other sources. This compound and some of its derivatives possess diverse activities including anticancer, anti-inflammatory, antioxidant , antibacterial and antifungal amongst others. Hence, the import of this study.
objectives: The growing concerns about the deleterious actions of free radical oxygenated species (FROS) in the human body have become a huge concern to scientific world. These chemical species continually devastate the human cells, tissues and organs leading to different patho-physiological conditions and neurodegenerative disorders. Also, the noticeable microbial resistance to antibiotics and antifungal drugs have prompted the search for lead compound(s) with the aim of chemically modifying its/their molecular structure(s) or synthesizing other compounds from reactions involving them such as Schiff base synthesis. The search for novel pharmaceutically active compounds with the aim of ameliorating these conditions led to the choice of vanillin.
Methodology: Vanillin was subjected to the Schiff base synthesis. It was reacted separately with amines (aromatic and aliphatic amine) leading to the bases in the presence of acid. The melting points, refractive indices and optical rotations of the vanillin and the Schiff bases were obtained. The antioxidant activity (IC50) of the lead compound and bases was determined employing the DPPH (2, 2-diphenyl-1-picrylhydrazyl hydrate) bench-top assay test. Comparison of the obtained antioxidant activities was done to determine if any improvements could be noticed in the synthesized bases. Also, the agar-in-hole diffusion method was adopted for screening vanillin and the synthesized bases against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeriginosa and Candida albicans for antibacterial and antifungal activities respectively.
Results: The identities of the synthesized Schiff bases have been revealed to be vanillyl butyl imine (W) a new ketimine referred to by the trivial name-Walatimine and vanillin-2,4-dinitrophenyl hydrazone (Vdnp) respectively using a combination of physico-chemical determinations and IR spectral technique. Vanillin  and (W) demonstrated  marginal antioxidant activity of IC50  of  0.52 and 0.50 µg/mL respectively while Vdnp gave a remarkably significant IC50  of  0.48 and which compare favourably with 0.46 µg/mL elicited by Vitamin C (a standard antioxidant drug). The antibacterial and antifungal activities elicited by both W and Vdnp were concentration-dependent. Furthermore, Vdnp was comparably more bacteriostatic than W against the test bacteria though it was inactive against Ps. aeriginosa. However, vanillyl butyl imine (W) was slightly more anti-candidal against C.  albicans than vanillin-2,4-dinitrophenyl hydrazone (Vdnp).
Conclusion: The results from this study indicate that vanillin-2,4-dinitrophenyl hydrazone (Vdnp)  obtained from the condensation reaction of vanillin and an aromatic amine affords a comparably better antioxidant activity than W obtained from vanillin reacting with an aliphatic amine. Both W and Vdnp demonstrated remarkable antibacterial and antifungal activities hence, these two synthesized Schiff bases can be lead candidate compounds in the search for newer and more efficacious antioxidant and antimicrobial agents and in further structural activity relationship studies (SARS) and as well as in formulation studies in drug development.