Design and synthesis of phenolic Mannich base hydrazide-hydrazone hybrids

What is it about?

Vanillic acid, a naturally occurring phenolic compound, is well known for its antioxidant properties. In this study, a series of vanillic acid-based Mannich base hydrazide derivatives and their corresponding hydrazones were synthesized, and characterized using different spectroscopic techniques. The biological activity of the synthesized derivatives was further investigated using in vitro antioxidant and anticancer assays. In the DPPH and ABTS assays, compound 3g displayed the most potent antioxidant activity with IC50 values of 27.43 μM and 0.82 μM, respectively. Overall, hydrazide derivatives demonstrated higher activity than their corresponding hydrazones. Notably, all compounds (IC50 values 0.82 to 5.09 μM) displayed superior antioxidant activity relative to the standard (IC50 value 14.8 μM) in the ABTS assay. Owing to their superior antioxidant activities, anti-breast cancer activity was estimated against MDA-MB-231 and MCF-7 cells and the tested compounds have displayed moderate cytotoxicity. Further, drug-likeliness, ADME-toxicity studies were investigated. Furthermore, DFT studies were conducted for two of the identical compounds 4a and 4g to understand the electronic properties governing their antioxidant activities.

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Why is it important?

all the synthesized compounds showed favorable drug-like properties, satisfying Lipinski's rule and Veber's rule. All the compounds followed decent pharmacokinetic properties. Toxicity studies predicted genotoxicity risks for some of the hydrazides and hydrazones, which would require genotoxicity tests before further testing.