Antibacterial, Anticandidal, and Antibiofilm Potential of Fenchone: In Vitro, Molecular Docking and In Silico/ADMET Study

Abstract

The aim of the present study is to investigate the effective antimicrobial and antibiofilm properties of fenchone, a biologically active bicyclic monoterpene, against infections caused by bacteria and Candida spp. The interactions between fenchone and three distinct proteins from Escherichia coli (β-ketoacyl acyl carrier protein synthase), Candida albicans (1, 3-β−D-glucan synthase), and Pseudomonas aeruginosa (Anthranilate-CoA ligase) were predicted using molecular docking and in silico/ADMET methods. Further, to validate the in-silico prediction, the antibacterial and antifungal potential of fenchone was evaluated against E. coli, P. aeruginosa, and C. albicans by determining minimum inhibitory concentration (MIC), minimum bacterial concentration (MBC), and minimum fungicidal concentration (MFC). The lowest MIC/MBC values of fenchone against E. coli and P. aeruginosa obtained was 8.3 ± 3.6/25 ± 0.0 and 266.6 ± 115.4/533.3 ± 230.9 mg/mL, respectively, whereas the MIC/MFC value for C. albicans was found to be 41.6 ± 14.4/83.3 ± 28.8 mg/mL. It was observed that fenchone has a significant effect on antimicrobial activity (p < 0.05). Our findings demonstrated that fenchone at 1 mg/mL significantly reduced the production of biofilm (p < 0.001) in E. coli, P. aeruginosa, and C. albicans by 70.03, 64.72, and 61.71%, respectively, in a dose-dependent manner when compared to control. Based on these results, it has been suggested that the essential oil from plants can be a great source of pharmaceutical ingredients for developing new antimicrobial drugs.

Keywords: antimicrobial activity; biofilm; essential oil; fenchone; molecular docking.

Figure 1

The 3D structure of modeled (a) Anthranilate-CoA ligase, (b) 1, 3-β–D-glucan synthase, and (c) β-ketoacyl acyl carrier protein synthase I (PDB:1FJ4).

Figure 2

Identification of protein structure of Anthranilate-CoA ligase (a) and 1, 3-β–D-glucan synthase (b) using ProSA.

Figure 3

Assessing the quality of predicted Anthranilate-CoA ligase (a), and 1, 3-β–D-glucan synthase (b) structure.

Figure 4

Interaction of β-ketoacyl acyl carrier protein synthase I with fenchone.

Figure 5

Interaction of Anthranilate-CoA ligase with fenchone.

Figure 6

Interaction of 1, 3-β–D-glucan synthase with fenchone.

Figure 7

MBC/MFC (mg/mL) results of fenchone oil against E. coli (A), MDR-PA (B) and C. albicans (C). The dosage of fenchone oil is numerically depicted as 1, 2, 3, 4, 5 and 6, which are 200, 100, 50, 25, 12.5 and 6.25 mg/mL, respectively.

Figure 8

Impaired biofilm formation of E. coli, MDR-PA, and C. albicans caused by fenchone treatment. The data is presented as average of three independent tests in triplicates with standard deviation. The asterisks (**) represent the significance as p < 0.001 against their control experiments by One-Way ANOVA-based Pairwise Multiple Comparison Procedures (Holm-Sidak method), whereas overall significance level = 0.05 was conductedon SigmaPlot 11.05 statistical analysis software.