Structure characteristics of flavonoids for heterocyclic aromatic amines inhibition using quantitative structure–activity relationship modeling

Abstract

The objective of this study was to investigate the structure characteristics of flavonoids that act as inhibitors for heterocyclic aromatic amines (HAAs) formation. Five quantitative structure–activity relationship models for predicting the inhibitory rates of HAAs (norharman, harman, PhIP, MeIQx, and 4,8‐DiMeIQx) were established using selected chemometric parameters (R2: 0.591–0.920), and indicated that the hydrophobicity, hydroxyl groups, and topological structure of flavonoids played important roles in the inhibition of HAAs formation. The 5,7‐dihydroxyls in meta‐position of the A‐ring and the 4′‐hydroxyl in the B‐ring of flavonoids were critical for the inhibitory effects of HAAs, whereas the introduction of 3‐hydroxyl and 3‐O‐glucoside in the C‐ring reduced the inhibitory effects. Catechin served as the most effective inhibitor of HAAs followed by luteolin and genistein. The study can bring us a broader idea for controlling the formation of HAAs according to the structure of flavonoids. Practical applications Heterocyclic aromatic amines (HAAs) are a class of organic substances with carcinogenic and mutagenic effect formed during the heating process of meat products. The formation of HAAs can be inhibited by adding natural antioxidants such as flavonoids to the meat during pretreatment. This inhibition is influenced by the unique structure of flavonoids. Thus, there has been an increasing demand to exploit the effective HAAs inhibitors from flavonoids by structure characteristics. Our study showed that the inhibitory effect of flavonoids on the formation of HAAs was mainly depended on their hydrophobicity, hydroxyl groups, and topological structure using the multiple QSAR models. Thus, effective HAAs inhibitors can be explored from dietary flavonoids according their structure characteristics.

Inhibitory effects of Chinese quince fruit proanthocyanidins with different polymerisation degrees on the formation of heterocyclic aromatic amines in chemical model systems

“…Specifically, the correlation coefficients between mean DP and individual HCAs were −0.799 for PhIP, −0.758 for harman and −0.697 for norharman, indicating that the mean DP significantly affects ( P < 0.05) the formation of HCAs. Proanthocyanidins with lower DPs could reduce HCAs due to the presence of more nucleophilic sites which benefit adduct formation (Zhao et al ., 2020). The result showed a negative linear dependent relationship between antioxidant abilities and HCA inhibition (Table 5), but none of them were significant ( R 2 < −0.370, P > 0.05).…”

Diversity of the Chemical Profile and Biological Activity of Capsicum annuum L. Extracts in Relation to Their Lipophilicity

“…In the case of single compounds, many algorithms have been developed that help in the theoretical determination of the activity spectrum. Based on the QSAR analysis, the physical and chemical properties of compounds are calculated and their bioavailability and biological activity are estimated [ 15 , 16 ]. It has been found that lipophilicity is one of the most important physicochemical properties that influences the biological activity of compounds [ 17 ].…”

Formation and Prediction of PhIP, Harman, and Norharman in Chemical Model Systems Containing Epicatechin under Various Reaction Conditions

“…The ability of epicatechin to mitigate HA formation may also be related with its scavenging capacities of the free radical and reactive carbonyl, which are highly related to the formation of HAs . Zhao also reported that 10 mM epicatechin exhibited 44.01, 31.13, and 78.04% inhibitory effects on the formation of PhIP, Harman, and Norharman, respectively, in the chemical model system that was heated at 175 °C for 30 min.…”

“… The establishment of chemical model systems of PhIP, Harman, and Norharman was carried out according to the literature with slight modifications. , Briefly, for PhIP, 0.4 mmol phenylalanine, 0.4 mmol creatinine, 0.4 mmol glucose, and 0.2 mmol epicatechin were added into 25 mL screw cap-sealed reaction vials (Strg Vial Kit, 40 mL, 28 × 95 Amber, 24-414 Cap, Agilent, USA); then, 4 mL of diethylene glycol containing 14% of distilled water was added, and citric acid-phosphate buffer was used to adjust the pH of the mixed solution using a pH meter (FE28-Micro, Mettler Toledo, Switzerland) under magnetic stirring (EMS-19, Tianjin Honour lnstrument Co., Ltd., China), which was finally stirred evenly. For Harman and Norharman, 0.4 mmol tryptophan, 0.4 mmol glucose, and 0.2 mmol epicatechin were put into 25 mL screw cap-sealed reaction vials; then, 4 mL of diethylene glycol containing 14% of distilled water was added, and citric acid-phosphate buffer was used to adjust the pH of the mixed solution, which was finally stirred evenly.…”

“…Naringenin, kaempferol, quercetin, genistein, and luteolin were reported to inhibit the formation of HAs in roasted beef patties; 12 chlorogenic acid, however, promoted the HA formation, 13 suggesting that different types of polyphenols have different inhibitory effects on the formation of HAs. Zhao 14 revealed that the topological structure of polyphenols played crucial roles in the inhibition of HA formation and indicated that epicatechin had a significant inhibitory effect on the formation of PhIP, Harman, and Norharman in chemical model systems. The presence of catechol or the o-trihydroxyl system and the phenolic carbons with a high electronic density 15 in the structure of epicatechin endowed it with potential for free-radical and reactive carbonyl scavenging activities.…”