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. 2024 Apr 18:12:1372560.
doi: 10.3389/fchem.2024.1372560. eCollection 2024.

Isolation of quinic acid from dropped Citrus reticulata Blanco fruits: its derivatization, antibacterial potential, docking studies, and ADMET profiling

Heena  1 , Sonia Kaushal  1 , Vishaldeep Kaur  1 , Harsh Panwar  2 , Purshotam Sharma  3 , Raman Jangra  3
Affiliations

Isolation of quinic acid from dropped Citrus reticulata Blanco fruits: its derivatization, antibacterial potential, docking studies, and ADMET profiling

Heena et al. Front Chem. .

Abstract

Citrus reticulata dropped fruits are generally discarded as waste, causing environmental pollution and losses to farmers. In the present study, column chromatography has been used to isolate quinic acid (1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid) from the ethyl acetate fraction of a methanol extract of citrus fruits dropped in April. Quinic acid is a ubiquitous plant metabolite found in various plants and microorganisms. It is an important precursor in the biosynthesis of aromatic natural compounds. It was further derivatized into 3,4-o-isopropylidenequinic acid 1,5-lactone (QA1), 1,3,4,5-tetraacetoxycyclohexylaceticanhydride (QA2), and cyclohexane-1,2,3,5-tetraone (QA3). These compounds were further tested for their antibacterial potential against the foodborne pathogens Staphylococcus aureus, Bacillus spp., Yersinia enterocolitica, and Escherichia coli. QA1 exhibited maximum antibacterial potential (minimum inhibitory concentration; 80-120 μg/mL). QA1 revealed synergistic behavior with streptomycin against all the tested bacterial strains having a fractional inhibitory concentration index ranging from 0.29 to 0.37. It also caused a significant increase in cell constituent release in all the tested bacteria compared to the control, along with prominent biofilm reduction. The results obtained were further checked with computational studies that revealed the best docking score of QA1 (-6.30 kcal/mol, -5.8 kcal/mol, and -4.70 kcal/mol) against β-lactamase, DNA gyrase, and transpeptidase, respectively. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis revealed that the drug-like properties of QA1 had an ideal toxicity profile, making it a suitable candidate for the development of antimicrobial drugs.

Keywords: biofilm; citrus reticulata; docking; dropped citrus fruits; lactone; quinic acid.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Synthetic routes of target compounds; QA1 (A), QA2 (B), and QA3 (C) from QA.
FIGURE 2
FIGURE 2
Zone of inhibition by QA1 against E. coli (i), Bacillus spp. (ii), Staphylococcus aureus= (iii), and Y. enterocolitica (iv) @ 250 μg/mL (A), 500 μg/mL, (B), 1,000 μg/mL (C), and 1,500 μg/mL (D).
FIGURE 3
FIGURE 3
MIC values (µg/mL) of compounds.
FIGURE 4
FIGURE 4
Effect of QA and derivatives on the leakage of cellular components in the tested bacterial strains.
FIGURE 5
FIGURE 5
Comparison of the binding pocket of the cognate ligand clorobiocin in (A) the crystallized form of DNA gyrase (PDB Code: 1KZN) and (B) the computationally docked complex. Three of the six analyzed ligands occupy the same binding pocket (C). Structural superposition of the crystallized form (green stick) and docked form (gray stick) of the ligand.
FIGURE 6
FIGURE 6
Binding pocket of streptomycin with transpeptidase (PDB id: IMWT).
FIGURE 7
FIGURE 7
Binding pocket of ampicillin with ß-lactamase (PDB id: 6BU3).
FIGURE 8
FIGURE 8
Representation of the docked structures of the complexes of DNA gyrase with the ligands quinic acid (QA), 3,4-o-isopropylidenequinic acid-1,5-lactone (QA1), 1,3,4,5-tetraacetoxycyclohexyla ceticanhydride (QA2), and cyclohexane-1,2,3,5-tetraone (QA3).
FIGURE 9
FIGURE 9
Representation of the docked structures of the complexes of transpeptidase with the ligands quinic acid (QA), 3,4-o-isopropylidenequinic acid-1,5-lactone (QA1), 1,3,4,5-tetraacetoxycyclohexyla ceticanhydride (QA2), and cyclohexane-1,2,3,5-tetraone (QA3).
FIGURE 10
FIGURE 10
Representation of the docked structures of the complexes of ß-lactamase with the ligands quinic acid (QA), 3,4-o-isopropylidenequinic acid-1,5-lactone (QA1), 1,3,4,5-tetraacetoxycyclohexylacetic anhydride (QA2), and cyclohexane-1,2,3,5-tetraone (QA3).
FIGURE 11
FIGURE 11
Radial plots of drug likeliness properties of compounds.
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