Bioevaluation and molecular docking analysis of novel phenylpropanoid derivatives as potent food preservative and anti-microbials

Abstract

Novel derivatives were synthesized using natural scaffold, like phenylpropanoids C₆-C₃ backbone to reduce unfavorable browning of food due to tyrosinase and oxidative spoilage. Most of the compounds displayed mushroom tyrosinase inhibition better than kojic acid. Compound CE48 exhibited better anti-tyrosinase (IC₅₀-29.64 μM) and antioxidant (EC₅₀-12.67 μM) activity than the reference compounds, kojic acid (IC₅₀-50.30 μM) and ascorbic acid (EC₅₀-14.55 μM), respectively. Compounds SAM30, SE78, 11F, and CE48 showed better anti-B. subtilis, anti-S. aureus, and anti-A. niger activity, respectively, compared to their parents. Molecular docking studies between inhibitors and mushroom tyrosinase corroborated the experimental reports, except SAM30 (glide score - 8.117) and SE78 (glide score - 6.151). In silico absorption, distribution, metabolism, excretion/toxicity (ADME/T) and toxicological studies of these newly synthesized compounds exhibited acceptable pharmacokinetic and safety profiles, like good aqueous solubility (- 3.34 to - 7.57), low human oral absorption (e.g., SAM30, SE78, FAM34), low gut-blood barrier permeability [36.67-209.88 nm/s in Cancer coli-2 (Caco-2) cells] and [19.45-91.51 nm/s in Madin-Darby Canine Kidney (MDCK) cells], low blood-brain barrier penetration, non-mutagenicity, and non-carcinogenicity. Interestingly, the synthesized compounds also possessed multifunctional properties, like microbial growth inhibitor, free radicals scavenger, and it also prevented browning of raw fruits and vegetables by inhibiting tyrosinase enzyme.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-020-02636-0.

Keywords: Antimicrobial; Antioxidant; Molecular docking; Phenylpropanoids; Tyrosinase inhibitor.

Fig. 1

Synthesis routes of the phenylpropanoid derivatives. The amide derivatives SAM30 and FAM34 were obtained by treatment of sinapoyl chloride (SC) and feruloyl chloride (FC) with appropriate amine in the presence of diethyl ether (a, b). Compounds SE78, 11F, and CE48 were obtained by the general reaction of SC, FC, and caffeoyl chloride (CC) with appropriate alcohol and diethyl ether (c, d, e)

Fig. 2

Binding interactions of the newly synthesized phenylpropanoid derivatives with mushroom tyrosinase. a, b represents the interaction of SA derivatives SAM30 and SE78; C-D represents the interaction of FA derivatives 11F and FAM34; and E depicts CA derivative CE48 interaction with tyrosinase (PDB code: 2Y9W). Ligands are represented in brown ball-and-stick model. Two red spheres represent the copper atoms. Hydrogen bond interactions are presented in pink dotted lines, pi–cation interaction in red dotted line and green dotted line represent the pi–pi stacking interaction