From: Review on plant antimicrobials: a mechanistic viewpoint
Class of naturally compound | Compound | Conc. | Mechanisms of action | Active against | Findings | Reference |
---|---|---|---|---|---|---|
Alkaloids | Reserpine | 100 mg/L | Efflux pump inhibitor | Staphylococcus sp., Streptococcus sp. and Micrococcus sp. | • Reducing the (MIC) of antibiotics • In vitro model | [60] |
Piperine | 100μg/mL | Efflux pump inhibitor | Methicillin resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus | • In vitro model | [46] | |
Berberine | 4 mM | Cell division inhibitor, Protein and DNA synthesis inhibitor | Escherichia coli Candida albicans | • In vitro model | ||
Chanoclavine |  | Efflux pump inhibitor | E. coli | • Reducing the MIC of tetracycline up to 16-folds | [70] | |
Solasodine | 32μg/mL | Destruction of bacterial membrane | C. albicans | • Potent fungicidal activity • In vitro model | [197] | |
Conessine | 20 mg/L | Efflux pump inhibitor | Pseudomonas aeruginosa | • Active against RND family pump | [71] | |
Evocarpine | 5 mg/mL | Â | Mycobacterium tuberculosis | Â | [198] | |
Tomatidine |  | ATP synthase inhibitor | Listeria, Bacillus and Staphylococcus spp | • In vitro model • Its analog possess bactericidal activities | ||
Lysergol |  | Efflux pump inhibitor | E. coli | • Lowering the dose of antibiotics | [201] | |
Organosulfur | Allicin |  | Sulfhydryl-dependent enzyme inhibitor, DNA and protein synthesis inhibitor | Staphylococcus epidermidis, P. aeruginosa, Streptococcus agalactiae | • In the gas phase active against antibiotic resistant strains | [83] |
Ajoene |  | Sulfhydryl-dependent enzyme inhibitor | Campylobacter jejuni, Streproproteus, Staphylococcus and E. coli | • Zone inhibition method • More potent than allicin | [88] | |
Sulforaphane |  | Destruction of bacterial membrane, ATP synthase inhibitor, DNA and protein synthesis inhibitor | E. coli | • Did not destroy the membrane integrity directly | [202] | |
Berteroin | Range of 1 – 16 μg/mL |  | Helicobacter pylori |  | [108] | |
Hirsutin | Range of 8 – 16 μg/mL |  | P. aeruginosa and Bacillus cereus | • Having antifungal and antimicrobial activities. | [203] | |
Alyssin | Â | Â | H. pylori | Â | [108] | |
Erysolin | Range of 4 – 32 μg/mL |  | H. pylori |  | [108] | |
Allyl isothiocyanate, Benzyl isothiocyanate and Phenethyl isothiocyanate |  |  | Bacillus subtilis, S. aureus, S. epidermidis, Enterococcus faecalis, Salmonella typhimurium, Enterobacter aerogenes, Enterobacter cloacae, and E. coli | • Show antibacterial activity against foodborne and resistant pathogens. • AITC was the major ITC in the stem and leaf of R. sativus | [204] | |
Phenolic compounds | Resveratrol | 0.064, 0.313 mg/mL | Efflux pump inhibitor | Mycobacterium smegmatis, Campylobacter jejuni | • Reduced MIC value of antibacterial agent against resistant strain | |
Baicalein | 64, 128, 64 μg/mL | Efflux pump inhibitor | M. smegmatis, MRSA, C. albicans | • Reduced MIC value of antibacterial agent against resistant strain | ||
Biochanin A | 256 μg/mL, no inhibitory effect, 12 μM | Efflux pump inhibitor | M. smegmatis, MRSA, Chlamydia spp. | • Reduced MIC value of antibacterial agent against resistant strain | ||
Formononetin | 256 μg/mL | Efflux pump inhibitor | M. smegmatis | • Reduced MIC value of antibacterial agent against resistant strain | [113] | |
Luteolin | 32 μg/mL | Efflux pump inhibitor | Mycobacteria spp. | • Reduced MIC value of antibacterial agent against resistant strain | ||
Kaempferol | 125, 128-256 μg/mL | Efflux pump inhibitor | MRSA, C. albicans, | • Reduced MIC value of antibacterial agent against resistant strain | ||
 | Rigidifing bacterial membrane | E. coli |  | [139] | ||
Kaempferol rhamnoside | 1.56 μg/mL | Efflux pump inhibitor | S. aureus | • Increased antimicrobial activity of ciprofloxacin | [128] | |
Myricetin | 32 μg/mL | Efflux pump inhibitor | M. smegmatis |  | [113] | |
Rhamentin | 19-75 μg/mL | Efflux pump inhibitor | S. aureus |  | [129] | |
Quercetin | 75 μg/mL | Efflux pump inhibitor | S. aureus |  | [129] | |
48.5 and 19.9μM | d-Alanine:d-alanine ligase | H. pylori and E. coli |  | [144] | ||
Chrysosplenol-D | 25 μg/mL | Efflux pump inhibitor | S. aureus | • Inhibited NorA EP in the presence of subinhibitory concentrations of berberine | [122] | |
Chrysoplentin | 6.25 μg/mL | Efflux pump inhibitor | S. aureus | • Inhibited NorA EP in the presence of subinhibitory concentrations of berberine | [122] | |
Silybin | Â | Efflux pump inhibitor | S. aureus | Â | [124] | |
Biochanin A | 10 μg/mL | Efflux pump inhibitor | S. aureus | • Reduced the expression of NorA protein | [123] | |
Genistein | 10 μg/mL | Efflux pump inhibitor | S. aureus |  |  | |
Orobol | 10 μg/mL | Efflux pump inhibitor | S. aureus |  |  | |
4′,6′-Dihydroxy-3′,5′-dimethyl-2′-methoxychalcone | 10 μg/mL | Efflux pump inhibitor | S. aureus | • Reduced MIC of erythromycin from 0.4 to 0.1 μg/mL | [130] | |
4-phenoxy-4′-dimethylamino ethoxychalcone | 9 μM | Efflux pump inhibitor | S. aureus | • Equipotent to reserpine | [131] | |
4-dimethylamino-4′-dimethylamino ethoxychalcone | 7.7 μM | Efflux pump inhibitor | S. aureus | • Equipotent to reserpine | [131] | |
Bergamottin epoxide | 35.7 μg/mL | Efflux pump inhibitor | MRSA | • Resulted in the 20-fold reduction in MIC value of norfloxacin | [168] | |
5,7-dihydroxy-6-(2-methylbutanoyl)-8-(3-methylbut-2-enyl)-4-phenyl-2H-chromen-2-one | 8 μg/mL | Efflux pump inhibitor | MRSA |  | [168] | |
5,7-dihydroxy-8-(2-methylbutanoyl)-6-(3-methylbut-2-enyl)-4-phenyl-2H-chromen-2-one | 8 μg/mL | Efflux pump inhibitor | MRSA |  |  | |
Epigallocatechin gallate | 1-10 μM | DNA gyrase | - |  | [134] | |
200 μM | Beta-ketoacyl-[acyl carrier protein] reductase (FabG) | E. coli |  | [141] | ||
64 μg/mL | Inhibition of dihydrofolate reductase | Stenotrophomonas maltophilia |  | [148] | ||
Chebulinic acid | Â | DNA gyrase | M. tuberculosis | In silico | [135] | |
3-p-Trans-coumaroyl-2-hydroxyquinic acid | 2.5-10 mg/mL | Damage to the cytoplasmic membrane | S. aureus | • Active against eleven food-borne pathogens | [137] | |
p-Coumaric acid | Â | Damage to the cytoplasmic membrane | Oenococcus oeni and Lactobacillus hilgardii | Â | [138] | |
Apigenin | 132.7 and 163.0 μM | d-Alanine:d-alanine ligase | H. pylori and E. coli | • Reverse inhibitor and competitive with ATP | [144] | |
Sophoraflavanone B | 15.6-31.25 μg/mL | Direct interaction with peptidoglycan | MRSA | - | [145] | |
Naringenin | 256 μg/mL | Beta-Ketoacyl acyl carrier protein synthase (KAS) III | E. faecalis | • Showed activity against vancomycin resistance E. faecalis | [140] | |
Eriodictyol | 256 μg/mL | Beta-Ketoacyl acyl carrier protein synthase (KAS) III | E. faecalis | • Showed activity against vancomycin resistance E. faecalis | [140] | |
Taxifolin | 128 μg/mL | Beta-Ketoacyl acyl carrier protein synthase (KAS) III | E. faecalis | • Showed activity against vancomycin resistance E. faecalis | [140] | |
Sakuranetin | 2.2 μM | FabZ | H. pylori |  | [142] | |
3,6-Dihydroxyflavone | 16-32 μM | Beta-Ketoacyl acyl carrier protein synthase (KAS) III and I | E. coli | • High binding affinity with KAS III | [109] | |
Curcumin | 13.8 μg/mL | Sortase A | S. aureus | • No growth inhibitory activity | [149] | |
25-100 μM | leaky membrane | S. aureus and E. coli | • Broad spectrum activity | [143] | ||
Morin | 39.37 and 8.54 μM | Sortase A and B | S. aureus | • Reduced clumping activity | [150] | |
4′,7,8-trihydroxyl-2-isoflavene | 0.85 μM | urease inhibitor | H. pylori | • 20-fold lower than acetohydroxamic acid | [147] | |
Coumarin | Aegelinol | 16 μg/mL | DNA gyrase inhibitor | Salmonella enterica serovar Typhi, Enterobacter aerogenes, Enterobacter cloacae, S. aureus | • Higher activity against Gram-negative bacteria than Gram-positive ones particularly Salmonella thypii | [157] |
Dose dependent inhibition between 5 and 25 μg/mL | H. pylori | |||||
Agasyllin | 32 μg/mL | DNA gyrase inhibitor | S. enterica serovar Typhi, E. aerogenes, E. cloacae, S. aureus | • Higher activity against Gram-negative bacteria than Gram-positive ones particularly Salmonella thypii | [157] | |
Dose dependent inhibition between 5 and 25 μg/mL | H. pylori | |||||
4′-senecioiloxyosthol | 5 μg/mL | DNA gyrase inhibitor | B. subtilis | • 6-fold more active against B. subtilis ATCC 9372 than that of xanthotoxin | [158] | |
Osthole | 125 μg/mL | DNA gyrase inhibitor | B. subtilis, S. aureus, K. pneumoniae, MSSA | - | [158] | |
Asphodelin A 4′-O-β-D-glucoside | Range of 128–1024 μg/mL | DNA gyrase inhibitor | S. aureus, E. coli, P. aeruginosa, C. albicans, Botrytis cinerea | - | [160] | |
Asphodelin A | Range of 4–128 μg/mL | DNA gyrase inhibitor | S. aureus, E. coli, P. aeruginosa, C. albicans, B. cinerea | - | [160] | |
Clorobiocin | - | DNA gyrase inhibitor | - | • noviosyl sugar moiety is essential for biological activity • mutations at Arg136 of GyrB in E. coli results in coumarin-resistant | [161] | |
Novobiocin | - | DNA gyrase inhibitor | - | • noviosyl sugar moiety is essential for biological activity • mutations at Arg136 of GyrB in E. coli results in coumarin-resistant | [161] | |
Coumermycin A1 | - | DNA gyrase inhibitor | - | • noviosyl sugar moiety is essential for biological activity • mutations at Arg136 of GyrB in E. coli results in coumarin-resistant | [161] | |
Bergamottin epoxide | - | Efflux pump inhibitor | MSRA | • 20-fold reduction in the MIC value of norfloxacin against MRSA | [169] | |
6-Geranyl coumarin | No inhibitory effect | Efflux pump inhibitor | S. aureus | • Reduced the MIC for tetracycline and norfloxacin by 2 times | [170] | |
Galbanic acid | No inhibitory effect | Efflux pump inhibitor | MDR clinical isolates of S. aureus | • Reduced MIC range of ciprofloxacin and tetracycline from 10-80 μg/ml to 2.5-5 μg/ml | [171] | |
Terpene | Farnesol | MBC = 20 μg/mL | Cell membrane disturbance | S. aureus | • Caused the largest initial and total leakage of K+ ions between the tested terpene alcohols • These effects were dose-dependent | [174] |
Nerolidol | MBC = 40 μg/mL | Cell membrane disturbance | S. aureus | • After farnesol, caused the largest initial and total leakage of K+ ions between the tested terpene alcohols • These effects were dose-dependent | [174] | |
Dehydroabietic acid | - | Cell membrane disturbance | S. aureus | • Midpoint antibacterial concentration (GD50) for 24 h incubation was < 20 μg/mL | [178] | |
(4R)-(-)-carvone | - | Cell membrane disturbance | C. jejuni, Enterococcus faecium, E. coli | - | [182] | |
- | Inhibits the transformation of cellular yeast form to the filamentous form | C. albicans | - | [173] | ||
(4S)-(+)-carvone | - | Cell membrane disturbance | L. monocytogenes | - | [182] | |
- | Inhibits the transformation of cellular yeast form to the filamentous form | C. albicans | - | [173] | ||
Thymol | 49.37 μg/ml | Inhibits H(+)-ATPase in the cytoplasmic membrane, cell membrane disturbance, efflux pump inhibition | C. albicans | • Exhibited synergistic activity in combination with fluconazole | [183] | |
51.25 μg/ml | C. glabrata | |||||
70 μg/ml | C. krusei | |||||
200, 150, 125, 125, 400, 300, 100, 250, 500, 300, 450 μg/ml, respectively | A. niger, A. fumigatus, A. flavus, A. ochraceus, Alternaria alternata, Botrytis cinerea, Cladosporium spp., Penicillium citrinum, P. chrysogenum, Fusarium oxysporum, Rhizopus oryzae | • The most growth inhibition was related to Cladosporium spp. | [184] | |||
8, 10, 6.5, 5 μg/ml, respectively | E. coli, E. aerogenes, S. aureus, P. aeruginosa | • Antibacterial efficiency of free thymol was higher than its in situ activity within the Thymus capitatus leaves | [186] | |||
312 μg/ml | Salmonella typhimurium, S. enteritidis, S. saintpaul | • Reduced Biofilms of Salmonella spp. on polypropylene, but did not eliminate the adhered cells | ||||
Carvacrol | 50, 100, 100, 100, 350, 300, 100, 150, 125, 125, 200 μg/ml, respectively | Cell membrane disturbance, efflux pump inhibition | A. niger, A. fumigatus, A. flavus, A. ochraceus, Alternaria alternata, Botrytis cinerea, Cladosporium spp., Penicillium citrinum, P. chrysogenum, Fusarium oxysporum, Rhizopus oryzae, | • The most growth inhibition was related to Aspergillus spp. | [184] | |
8, 8, 7, 7 μg/ml, respectively | E. coli, E. aerogenes, S. aureus, P. aeruginosa | • Antibacterial efficiency of free carvacrol was higher than its in situ activity within the Thymus capitatus leaves | [186] | |||
156 μg/ml | S. typhimurium, S. enteritidis, S. saintpaul | • Reduced Biofilms of Salmonella spp. on polypropylene, but did not eliminate the adhered cells | [187] | |||
Eugenol | 400, 400, 450, 350, 500, 450, 350, 350, 400, 400, 350 μg/ml, respectively | Cell membrane disturbance | A. niger, A. fumigatus, A. flavus, A. ochraceus, Alternaria alternata, Botrytis cinerea, Cladosporium spp., Penicillium citrinum, P. chrysogenum, Fusarium oxysporum, and Rhizopus oryzae | • The most growth inhibition was related to Cladosporium spp. and Rhizopus oryzae | [184] | |
2 μg/mL | H. pylori | • Maintain the bactericidal activity at low pH levels. The microorganism did not show any resistance to it even after 10 passages in the presence of sub-MIC levels | [191] | |||
0.04% V/V in MHB | MRSA, MSSA | • Inhibited biofilm construction • Interrupted cell-to-cell communication • Eradicated the pre-established biofilms • Killed the bacteria in biofilms | [192] | |||
150-300 μg/mL | P. aeruginosa | • Had anti-virulence, anti-biofilm and biofilm eradication properties • Could synergistically enhance bactericidal effect of gentamicin on biofilm associated bacteria | [193] | |||
Menthol | 150, 150, 100, 100, 450, 400, 125, 100, 300, 200, 250 μg/ml, respectively | Cell membrane disturbance | A. niger, A. fumigatus, A. flavus, A. ochraceus, Alternaria alternata, Botrytis cinerea, Cladosporium spp., Penicillium citrinum, P. chrysogenum, Fusarium oxysporum, Rhizopus oryzae | • The most growth inhibition was related to Cladosporium spp. and Aspergillus spp. | [184] | |
Cinnamaldehyde | 2 μg/mL | Cell membrane disturbance | H. pylori | • Maintain the bactericidal activity at low pH levels. • The microorganism did not show any resistance to it even after 10 passages in the presence of sub-MIC levels | [191] | |
0.25 μL/mL | Cell membrane and metabolic activity disturbance | E. coli and S. aureus | - | [194] | ||
Ursolic acid | - | Cell membrane disturbance | E. coli | - | [190] | |
α-Amyrin | - | Cell membrane disturbance | E. coli | - | [190] |