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

Unlabelled: Novel derivatives were synthesized using natural scaffold, like phenylpropanoids C-C 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 (IC-29.64 μM) and antioxidant (EC-12.67 μM) activity than the reference compounds, kojic acid (IC-50.30 μM) and ascorbic acid (EC-14.55 μM), respectively. Compounds SAM30, SE78, 11F, and CE48 showed better anti-, anti-, and anti- 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.