Table 2 The strongest plant antimicrobial compounds reported in recent years

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

[51, 196]

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

Mycobacterium tuberculosis

[198]

Tomatidine

ATP synthase inhibitor

Listeria, Bacillus and Staphylococcus spp

• In vitro model

• Its analog possess bactericidal activities

[199, 200]

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

H. pylori

[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

[112-113]

Baicalein

64, 128, 64 μg/mL

Efflux pump inhibitor

M. smegmatis, MRSA, C. albicans

• Reduced MIC value of antibacterial agent against resistant strain

[113, 117, 205]

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

[113, 119-120]

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

[113, 206]

Kaempferol

125, 128-256 μg/mL

Efflux pump inhibitor

MRSA, C. albicans,

• Reduced MIC value of antibacterial agent against resistant strain

[126-127]

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

Efflux pump inhibitor

S. aureus

[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

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

Damage to the cytoplasmic membrane

Oenococcus oeni and Lactobacillus hilgardii

[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

[187-188]

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]