Aesculin based glucosamine-6-phosphate synthase inhibitors as novel preservatives for food and pharmaceutical products: in-silico studies, antioxidant, antimicrobial and preservative efficacy evaluation

Amit Lather,Sunil Sharma,Anurag Khatkar

doi:10.1186/s13065-021-00769-8

Abstract

BackgroundPresently available chemical based synthetic preservative have emerged with various side effects, so the aspiration of natural and side effect free novel preservative has been greatly increased. As the natural preservative exhibit poor side effect with improved preservative efficacy. The recent development in computational studies leads advancement in drug designing and discovery of novel glucosamine-6-phosphate synthase (G-6-P synthase) inhibition based natural antimicrobial preservatives. Here, selected aesculin derivatives were screened for G-6-P synthase inhibition via docking study and evaluated for antioxidant, antimicrobial, preservative efficacy as well stability study.ResultsModified aesculin derivatives were designed, synthesized and showed potent G-6-P synthase inhibition with remarkable antimicrobial, antioxidant, preservative efficacy and stability study. The molecular docking with target pdb id 1moq from G-6-P synthase resulted with better dock score and energy for compound 1 as compared to standard drugs streptomycin, ciprofloxacin, ampicillin and fluconazole, that supported the wet lab results. Among the synthesized compounds, the compound 1 possessed good antioxidant activity as compared to standard L-ascorbic acid. The resultant data for antimicrobial activity of aesculin derivatives revealed compound 1 as the most potent antimicrobial compound as compared to the standard drugs streptomycin, ciprofloxacin, ampicillin and fluconazole. While compound 2 showed better antimicrobial activity as compared to streptomycin, ciprofloxacin, ampicillin. The preservative efficacy test for compound 1 in aloe vera juice and white lotion USP has been showed the log CFU/mL values within the prescribed limit of USP standard and results were comparable to standard sodium benzoate, ethyl paraben and propyl paraben. Compound 1 has been found to be within prescribed limit of stability study over six month.ConclusionCompound 1 showed the potent G-6-P synthase inhibitory, antioxidant, antimicrobial, preservative efficacy and stability study results as compared to standard drugs taken. The results have found comparable to molecular docking results, and this final compound may be used as new preservatives for food and pharmaceutical products. Moreover, the mechanistic insight into the docking poses was also explored by binding interactions of aesculin derivatives inside the pdb id 1moq. These results also supported the results for novel synthesized G-6-P synthase inhibitors.Graphical abstract

Highlights

Glucosamine-6-Phosphate synthase (G-6-P synthase) catalyzed the first step in hexosamine biosynthesis and converted Fructose-6-Phosphate (Fru-6-P) into GlcN6-P (Glucosamine-6-Phosphate), a precursor of Uridine Diphosphate N-acetyl glucosamine (UDP-NAG)
G-6-P synthase offers a potential target for the action of antimicrobial agents and it has attracted the interest of several researchers [1]
The 3D-crystallographic structure of enzyme involved in microbial cell wall synthesis i.e. G-6-P synthase is available and can be explored as a novel target for search of better antimicrobial compounds [5]

Summary

Introduction

Glucosamine-6-Phosphate synthase (G-6-P synthase) catalyzed the first step in hexosamine biosynthesis and converted Fructose-6-Phosphate (Fru-6-P) into GlcN6-P (Glucosamine-6-Phosphate), a precursor of Uridine Diphosphate N-acetyl glucosamine (UDP-NAG). The 3D-crystallographic structure of enzyme involved in microbial cell wall synthesis i.e. G-6-P synthase is available and can be explored as a novel target for search of better antimicrobial compounds [5]. The phytoconstituents of plants with reported antimicrobial efficacy may be explored using the molecular docking and large number of molecules can be screened within a short time [6]. Have been reported for their antimicrobial efficacy [7,8,9] Similar to this there is a scope to explore the other selected phytoconstituents for discovery of safe and better G-6-P synthase inhibitors. The recent development in computational studies leads advancement in drug designing and discovery of novel glucosamine-6-phosphate synthase (G-6-P synthase) inhibition based natural antimicrobial preservatives. Selected aesculin derivatives were screened for G-6-P synthase inhibition via docking study and evaluated for antioxidant, antimicrobial, preservative efficacy as well stability study

Methods

Results

Conclusion