Table 4.

Bacterial efflux pump inhibitors

Inhibitors	Efflux pump(s) targeted	Antibacterials with activity enhanced^a	References
Gram-negative bacteria
Arylpiperazines: 1-(1-naphthylmethyl)-piperazine and others.	RND pumps of A. baumannii, Citrobacter freundii, E. aerogenes, E. coli, K. pneumoniae, V. cholerae	FQ, MA, TC	[713, 719, 772–774]
Carbonyl cyanide m-chlorophenylhydrazone (CCCP)	Secondary transporters such as RND, MFS and MATE pumps	MA	[1]
Dipeptide amides (synthetic): Phe-Arg-β-naphthylamide (MC-207,110), MC-02,595, and MC-04,124	RND-type pumps of Gram-negative bacteria including Mex pumps of P. aeruginosa and AcrAB-TolC of E. coli	FQ, MA, plant antimicrobials	[1, 230, 356, 715, 718, 719, 773]
EA-371alpha and EA-371delta of Streptomyces	MexAB-OprM of P. aeruginosa	LF	[1]
Extracts of Berberis aetnensis	E. coli, P. aeruginosa, S. aureus pumps not reported	CP	[775]
Extracts of Commiphora molmol, Centella asiatica, Daucus carota, Citrus aurantium and Glycyrrhiza glabra	AcrAB-TolC of E. coli	CM, NA, TC	[697]
Phenothiazines	E. coli pumps	MA	[711]
Pyridopyrimidine series	MexAB-OprM of P. aeruginosa	AZ, FQ,	[703–707]
Quinoline derivatives	AcrAB-TolC of E. aerogenes, E. coli, K. pneumoniae	MA	[181, 189, 693, 776]
Tetracycline analogues	Tet pumps	TC	[1]
Thanatin	Pumps of E. aerogenes and K. pneumoniae	CM, NF, TC	[777]
Gram-positive bacteria
3-aryl piperidines	MepA and NorA of S. aureus	FQ	[778]
Baicalein (trihydroxy flavone)	Tet(K) and unidentified pump(s)/mechanisms of S. aureus	AP, CA, OX, TC	[779]
Berberine	NorA of S. aureus	FQ	[1]
Catechin gallates: epicatechin gallate and epigallocatechin gallate	NorA and Tet(K) of S. aureus	NF, TC	[722, 780, 781]
Diterpenes: abietane (carnosic acid and carnosol), isopimarane and geranylgeranyl diterpenes	Msr(A) and Tet(K) of S. aureus	EM, TC	[782, 783]
Diterpenes: ferruginol, pisiferol, 5-epipisiferol, formosanoxide, trans-communic acid, torulosal, the sesquiterpene oplopanonyl acetate and the germacrane 4 beta-hydroxygermacra-1(10)-5-diene	NorA of S. aureus	OX	[784]
Extracts of Mezoneuron benthamianum and Securinega virosa	S. aureus pumps	EM, FQ, TC	[785]
Extracts of Mirabilis jalapa Linn.: N-trans-feruloyl 4′-O-methyldopamine and synthetic N-trans-3,4-O-dimethylcaffeoyl tryptamine	NorA of S. aureus	NF	[786]
Extracts of Punica granatum	NorA of S. aureus	AP, CM, GM, OX, TC	[787]
Flavones: 5′-methoxyhydnocarpin	NorA of S. aureus	FQ	[1, 718]
Flavonolignans: flavonoid tricin and silybin	NorA of S. aureus	BB, FQ	[1, 788]
Fluoroquinolone derivatives	MepA and NorA of S. aureus	FQ	[789]
GG918 (synthetic)	Unidenitifed pump(s) of S. aureus (but known to target P-glycoprotein)	FQ	[790]
Grapefruit oil (coumarin, abergamottin epoxide and coumarin epoxide derivatives)	S. aureus pump(s) not reported	EB, NF	[791]
Indoles: 2-aryl-5-nitro-1H-indoles	NorA of S. aureus	BB	[792]
Indoles: 5-nitro-2-phenyl-1H-indole (INF55) and others	NorA of S. aureus	FQ	[1, 717]
Kaempferol glycoside from Herissantia tiubae	NorA of S. aureus	EB, FQ	[793]
Methoxylated flavones/isoflavones: chrysosplenol-D, chrysoplenetin, genistein, orobol and biochanin A, pterocarpan	NorA of S. aureus	BB, FQ	[794–796]
Oligosaccharides murucoidins and stoloniferin	NorA of S. aureus	NF	[797]
Penta-substituted pyridine: 2,6-dimethyl-4-phenyl-pyridine-3,5-dicarboxylic acid diethyl ester	MsrA of S. aureus	FQ	[709]
Phenothiazines: chlorpromazine and thioridazine	Unknown but may be associated with NorA, Erm(A) and Erm(B) of S. aureus	MA	[697, 711, 798–801]
Piperine: 1-piperoyl-piperidine and analogs	NorA of S. aureus	CP, EB, FQ	[714, 802]
Piperidine alkaloids: julifloridine, juliflorine and juliprosine	NorA of S. aureus	FQ	[702]
Polyacylated neohesperidosides	NorA of S. aureus	BB, FQ, RH	[803]
Polyacylated oligosaccharides: orizabins	NorA of S. aureus	NF	[804]
Porphyrin pheophorbide a	NorA of S. aureus	BB, FQ	[788]
Pyrrolo [1,2-a] quinoxaline derivatives (omeprazole analogues; synthetic)	NorA of S. aureus	NF	[805]
Reserpine (alkaloid)	Bmr of B. subtilis, EfrAB of E. faecalis, NorA and Tet(K) of S. aureus, PmrA and PatAB of S. pneuomoniae	FQ, TC	[1, 463]
Resin glycosides of Ipomoea murucoides (murucoidins, pescaprein and stoloniferin)	NorA of S. aureus	FQ	[797]
Spinosan A (arylbenzofuran aldehyde)	NorA of S. aureus	BB	[796]
Stilbene (phenolic metabolite)	NorA of S. aureus	BB, EM, TC	[708]
Totarol (phenolic diterpene)	NorA of S. aureus	EB, FQ	[806]
Mycobacteria
CCCP	M. tuberculosis	SM	[807]
Chlorpromazine	M. avium	EB, EM	[808]
Dipeptide amide (synthetic): Phe-Arg-β-naphthylamide	M. tuberculosis	FQ	[515]
Isoflavonoid (biochanin A), flavone (luteolin(and stilbene(resveratrol)	M. smegmatis	EB	[809]
Reserpine	M. smegmatis, M. tuberculosis	EB, FQ	[515, 809]
Thioridazine	M. avium, M. tuberculosis	EB, EM	[732, 801, 808]
Verapamil	M. avium, M. smegmatis, M. tuberculosis	EB, EM, SM	[807, 809]

AP=Ampicillin; AZ=aztreonam; BB=berberine; CA=cefmetazole; CM=chloramphenicol; CP=ciprofloxacin; FQ=fluoroquinolones; GM=gentamicin; LF=levofloxacin; MA=multiple antibacterials; NA=nalidixic acid; NF=norfloxacin; OX=oxacillin; RH=rhein; SM=streptomycin; TC=tetracyclines.