Synthesis and Antioxidative Activity of Piperine Derivatives Containing Phenolic Hydroxyl

Abstract

Piperine was used in this study in its raw form, and different steps, such as amide hydrolysis and amidation, were used to synthesize piperine derivatives containing a phenolic hydroxyl group. DPPH and ABTS free radical scavenging assays were used to assess piperine derivative antioxidant activities. We constructed an AAPH oxidative stress erythrocyte model to study the effect of piperine derivatives on the hemolysis rate of oxidatively damaged erythrocytes as well as the hemoglobin oxidation rate. This AAPH model was also used to determine piperine derivative effects on antioxidant enzyme activity and malondialdehyde (MDA) content. Results showed that spectroscopic methods could synthesize and identify piperine derivatives containing phenolic hydroxyl groups (H-1∼H-3). Moreover, DPPH and ABTS assay results showed that piperine derivative free radical clearance rates were higher compared with the parent compound. Additionally, piperine derivatives (H-1∼H-3) were found to provide protection to AAPH oxidatively damaged erythrocytes in their ability to inhibit AAPH-induced erythrocyte lysis, while hemoglobin oxidation was higher compared with the parent compound. Piperine derivatives may protect intracellular glutathione peroxidase (GSH-Px) antioxidant enzyme system activities, safeguarding against oxidative damage. This study synthesized novel piperine derivatives for use as potential antioxidant agent candidates.

Semi-Synthesis of N-Aryl Amide Analogs of Piperine from Piper nigrum and Evaluation of Their Antitrypanosomal, Antimalarial, and Anti-SARS-CoV-2 Main Protease Activities

“…The semi-syntheses of N-aryl piperamide analogs 3-5 were performed using piperic acid and amine reagents, including aniline, 2,4-dimethoxyaniline, and 2,5-dimethoxyaniline as the starting materials for amidation (Figure 1). Several amide synthetic conditions were employed, including the conversion of the acid motif to an activated acyl chloride by thionyl chloride or oxalyl chloride and the formation of highly reactive O-acylisourea derived from amide coupling reagents, such as dicyclohexylcarbodiimide and 1-ethyl-3-(3dimethylaminopropyl)carbodiimide (EDCI) in the presence of 4-dimethylaminopyridine [31][32][33][34]. However, these conditions did not deliver the desired N-aryl piperamides 4 and 5 possibly due to the resonance effects of both (3,4methylenedioxyphenyl)-penta-2,4-dienoyl moiety of piperic acid and dimethoxy substituted phenyl groups of amines, which resulted in the low reactivities of both electrophiles and nucleophiles, respectively.…”

Innovative Green Approach for Extraction of Piperine from Black Pepper Based on Response Surface Methodology

“…When NADESs have enough water, their viscosity and polarity vary, allowing researchers to modify their characteristics and make them appropriate extraction mediums for undesirable chemicals. Low extraction yields were explained by the weakened interactions between NADES and the targeted compound which occurred after the addition of 50% (v/v) water, according to Dai et al and others [45][46][47][48]. The viscosities of the NADESs were also found to be extremely temperature sensitive.…”

Black pepper: Chemical composition and biological activities

“…According to Qin et al [41], piperine showed the scavenging effect on DPPH and ABTS radicals. It is interesting that after structural modifications, piperine derivatives showed higher scavenging capacity on DPPH and ABTS radicals [41]. In a study by Zarai et al [42], piperine showed the weakest antioxidant activity compared to aqueous, ethanolic, methanolic, and ethyl acetate extracts.…”

“…Based on TLC-bioautography antioxidant results, piperine was qualitatively inactive as an antioxidant [40]. According to Qin et al [41], piperine showed the scavenging effect on DPPH and ABTS radicals. It is interesting that after structural modifications, piperine derivatives showed higher scavenging capacity on DPPH and ABTS radicals [41].…”