Anti-inflammatory and antioxidant activity of synthesized mannich base derivatives of (2e,6e)-2-[(4-hydroxy-3-methoxyphenyl)methylidene]-6-(phenyl methylidene)cyclohexan-1-one

Abstract

Objective: To further understand this compound, we synthesized and evaluated the antioxidant and anti-inflammatory activity of a series of its Mannich base derivatives. Methods: We synthesized the compounds via the previously reported Mannich reaction method. Their structures were elucidated by Fouriertransform infrared,1H-NMR,13C-NMR, and high-resolution mass spectra. The derivatives’ anti-inflammatory and antioxidant activities were tested using the inhibition of protein denaturation method and the 2,2-diphenyl-2-picrylhydrazyl free radical scavenging assay. Results: The IC50 values for the anti-inflammatory activity of the 2,6-dimethylmorpholine, pyrrolidine, 1-methylpiperazine, and dimethylamine Mannich base derivatives 2a–d were 10.67, 10.72, 37.75, and 1.93 μM, respectively; for (2E,6E)-2-({4-hydroxy-3-methoxyphenyl}methylidene)-6- (phenylmethylidene)cyclohexan-1-one (1), diclofenac sodium, and curcumin, the IC50 values were 56.29, 1.52, and 8.43 μM, respectively. The IC50 values for the antioxidant activity of compounds 2a–2d were 229.62, 57.29, 280.43, and 219.22 μM, respectively; for compound 1, quercetin, and curcumin, the IC50 values were 144.22, 27.28, and 26.45 μM, respectively. Conclusion: Substituting Mannich bases into (2E,6E)-2-[(4-hydroxy-3-methoxyphenyl) methylidene]-6-(phenylmethylidene)cyclohexan-1-one enhanced its anti-inflammatory activity, but lowered its antioxidant activity. Compound 2d, (2E,6E)-2-({3-[(dimethylamino)methyl]-4-hydroxy-5- methoxyphenyl}methylidene)-6-(phenyl methylidene)cyclohexan-1-one, exhibited potent anti-inflammatory activity comparable to diclofenac sodium and four times higher than curcumin. However, further investigation of this compound’s mechanism of action and toxicity is warranted.