1. Mechanism of Action |
Energy Disruption |
CCCP-Carbonyl cyanide chlorophenyl hydrazone |
MFS- tetA, tetB |
H. pylori, Klebsiella spp. |
Tetracycline |
[98, 99] |
Synthetic EPI- IITR08027 |
MATE- abeM |
E. coli, A. baumanii |
Fluoroquinolones |
[100] |
PAβN |
RND- mexAB-oprM, mexCD-oprJ, mexEF-oprN |
P. aeruginosa |
LevofloxacinErythromycinStreptomycin |
[90, 101] |
Competitive Inhibition |
Verapamil |
MATE- dinF and norM |
M. tuberculosis |
BedaquilineOfloxacin |
[102] |
1-(1-napthylmethyl)-piperazine (NMP) |
RND- acrAB, acrEF |
E. coli |
LevofloxacinRifampinChloramphenicol |
[103] |
2. Plant origin |
Alkaloids |
Reserpine (Rawfolia serpentia) |
MFS- norA, tetK, Bmr MATE- mepA |
S. aureusBacillus subtilisStreptococcus pneumoniae |
NorfloxacinTetracyclineCiprofloxacin |
[104] |
Piperine (Piper nigram) |
ABC transporters MFS- norA |
S. aureus, Mycobacterium tuberculosis |
CiprofloxacinRifampicin |
[105] |
Conessine (Holarrheaa antidysenterica) |
RND- adeIJK, mexAB-oprM |
Acinetobacter baumannii Rifampicin |
Novobiocin |
[91] |
Flavanoids |
Baicalein (Thymus vulgaris) |
MFS- tetK, norA |
Staphylococci |
TetracyclineCiprofloxacin |
[106, 107] |
5′-methoxy-hydnocarpin (Berberis fremontii) |
MFS- norA |
S. aureus |
TetracyclineNorfloxacinBerberine |
[108] |
Genistein (Isoflavone) |
MFS- norA |
S. aureus |
Berberine |
[109] |
Epigallocatechin gallate |
MFS- tetK |
StaphylococciCamphylobacter |
TetracyclineErythromycinCiprofloxacin |
[110] |
Polyphenols |
Curcumin (Curcuma longa) |
MFS- norA RND |
S. aureusP. aeruginosa |
NorfloxacinCiprofloxacinGentamicin |
[111, 112] |
Coumarin (Mesua ferrea) |
MFS- norA |
S. aureus |
NorfloxacinCiprofloxacin |
[113] |
Phenolic diterpenes |
Carnosic acid (Rosmarinus officinalis) |
ABC transporter msrA |
S. aureus |
Erythromycin |
[114] |
Monoterpenoid |
Carnosol (Rosmarinus officinalis) |
ABC transporter msrA MFS- tetK |
S. aureus |
Tetracycline |
[114] |
Geraniol (Helichrysum italicum) |
RND- acrAB-tolC |
Enterobacter aerogenes |
Chloramphenicol |
[115] |
Catharanthine (Catharanthus roseus) |
RND- mexAB-oprM |
P. aeruginosa |
TetracyclineStreptomycin |
[116] |
3. Synthetic origin |
Quinolone derivatives |
Pyridoquinolones |
RND- acrAB-tolC |
Enterobacter aerogenes |
Norfloxacin |
[117] |
Arylpiperidines and aryl piperazine derivatives |
Phenylpiperadines |
RND- acrAB-tolC |
E. coli |
Linezolid |
[118] |
Pyridopyrimidine and pyranopyridine derivatives |
D2 and D13-9001MBX2319 |
RND- mexAB-oprMRND- acrAB-tolC |
P. aeruginosaE. coli |
FluoroquinolonesFluoroquinolones |
[119, 120][121] |
Naphthyridine derivatives |
1,8-naphthyridines sulfonamide |
MFS- norA |
S. aureus |
NorfloxacinEthidium bromide |
[97] |
Boronic acid derivatives |
6-(3-Phenylpropoxy) pyridine-3-boronic acid |
MFS- norA |
S. aureus |
CiprofloxacinEthidium bromide |
[122] |
Indole derivatives |
3-amino-6-carboxyl-indole3-nitro-6-amino-indole |
RND- acrAB-tolC |
E. coli |
ChloramphenicolTetracyclineErythromycinCiprofloxacin |
[123, 124] |
4. Clinically approved drug |
Hypoglycemic biguanide drug |
Metformin |
RND- acrAB-tolC MATE- mdtK |
K. pneumoniae |
Ampicillin-sulbactamMeropenemAmikacin |
[125] |
Tyrosine kinase Inhibitor |
Nilotinib |
MFS- EmrD |
S. aureus |
Ciprofloxacin |
[86] |
Ergot alkaloid-vasoconstrictor |
Dihydroergotamine |
MFS- norA |
S. aureus |
Ciprofloxacin |
[86] |
5. Microbial origin |
|
EA-371α and EA-371d (fermentation extract of Streptomyces spp. |
RND- mexAB-oprM |
P. aeruginosa |
Levofloxacin |
[126] |