Table 1.

Small molecule QS inhibitors. Structures, origin, working concentrations, mechanisms and effects.

Structures of QS Inhibitors	Marine Bacterial Origins	Sources of the Bacteria	QS-Inhibitory Concentration	Anti-QS Working Mechanisms	Effects	References
Cyclic peptides and a linear peptide
Cyclo (Trp-Ser)	Rheinheimera aquimaris	Marine sediment surrounding the Yellow Sea in Qingdao, China	sub-MIC: 0.2 mg/mL	Probably interfere in the stability of LasR receptor	Suppress biofilm formation and QS-regulated pyocyanin and elastase activity in Pseudomonas aeruginosa	[59]
Cyclo-l-proline-l-tyrosine	Bacillus cereus	Marine sediment along the Rhode Island coastline	-	Possibly inhibit Vibrio sp. LuxR	-	[37]
Cyclo (l-leucyl-l-prolyl)	Bacillus amyloliquefaciens	Mangrove rhizosphere of Palk Strait, Bay of Bengal, India	sub-MIC: 100 μg/mL	-	Inhibit QS-controlled biofilm and virulence factors (prodigiosin, extracellular polymeric substance, protease, and lipase) production in uropathogen Serratia marcescens	[60,61]
Cyclo (l-Pro-l-Phe)	Marinobacter sp.	A hypersaline cyanobacterial mat from wadi Muqshin in Oman, off the Arabian Sea coast	sub-MIC: μM grade	Possibly compete with signal molecules AHLs and inhibit QS	-	[53]
Cyclo (l-Pro-l-isoLeu)
Cyclo (l-Pro-lLeu)
Ngercheumicin F (R = C11H21), Ngercheumicin G (R = C11H23), Ngercheumicin H (R = C13H25), Ngercheumicin I (R = C13H27) (Cyclodepsipeptides)	Photobacterium halotolerans	Mussel surface in the tropical Pacific	20 μg/mL	Interfere with agr QS	Reduce expression of virulence genes of hla (hemolysin) and rnaIII (an effector molecule) of agr QS in Staphylococcus aureus	[62]
Solonamide A (Fatty acid-l-Phe- d-Leu-d-Ala-l-Leu)	Photobacterium halotolerans	Mussel surface in the tropical Pacific	μg/mL–mg/mL	Possibly interfere with the agr QS system by competing with AIP for binding to sensor histidine kinase AgrC	Inhibit virulence gene expression of hla (hemolysin), rnaIII (an effector molecule of agr) and psmα (phenol soluble modulins) in Staphylococcus aureus, and reduce toxicity of S. aureus toward human neutrophils	[63,64]
Solonamide B (Fatty acid-l-Phe- d-Leu-d-Ala-l-Leu)
Linear dipeptide proline-glycine	Streptomyces sp.	Marine invertebrates from the western coast of India	sub-MIC: 0.1 mg/mL	-	Inhibit QS-mediated virulence factors (swarming, pyocyanin pigmentation, biofilm formation, rhamnolipid production, and Las A) in Pseudomonas aeruginosa	[32]
Amides
2-Methyl-N-(2′-phenylethyl) butyramide	Oceanobacillus sp.	Marine environment	sub-MIC: μg/mL grade	-	Inhibit pyocyanin production, elastase activity and biofilm formation of Pseudomonas aeruginosa	[65]
3-Methyl-N-(2′-phenylethyl)-butyramide
N-(2′-Phenylethyl)-isobutyramide	Halobacillus salinus	Sea grass sample from Point Judith Salt Pond, Rhode Island	sub-MIC: μg/mL grade	Possibly compete with AHLs for receptor binding	-	[66]
3-Methyl-N-(2′-phenylethyl)-butyramide
8-epi-Malyngamide C (8R) and malyngamide C (8S)	cyanobacterium Lyngbya majuscula	Off Bush Key, Florida	μM grade	-	-	[67]
Fatty Acids and phenol derivatives
cinnamic acid	Streptomyces sp.	Marine invertebrates from the western coast of India	sub-MIC: 0.1 mg/mL	-	Inhibit QS-mediated virulence factors (swarming, biofilm formation, LasA, pyocyanin and rhamnolipid production) in Pseudomonas aeruginosa	[32]
β-Hydroxy butyric acid (degradation product of PHB)	Brevibacterium casei (sources of PHB)	Marine sponge Dendrilla nigra	50 μg/mL (PHB)	Possibly by AHL degradation	Control biofilm formation, colonization capacity, motility and hemolysin activity of Vibrio sp.	[68]
Lyngbyoic acid	cyanobacterium Lyngbya cf. majuscula	Indian River Lagoon near Fort Pierce, Florida	μM–mM grade	Possibly inhibit lasR signaling by competing with AHL for binding LasR	Reduce pyocyanin and elastase (LasB) in Pseudomonas aeruginosa	[69]
Lyngbic acid	cyanobacterium	Corals from the Florida Keys and Belize	nM–μM grade	Compete with CAI-1 for binding to QS signal receptor CqsS	-	[70]
Pitinoic acid A	cyanobacterium similar to Lyngbya sp.	A channel at the north end of Piti Bay at Guam	sub-MIC: μM–mM grade	-	Inhibit expression of QS-related virulence factor LasB (elastase) and the pyocyanin in Pseudomonas aeruginosa	[71]
Phenol, 2,4-bis (1,1-dimethylethyl)	Vibrio alginolyticus	Red seaweed Gracilaria gracilis from the Karankadu coastal region of Palk Bay, India	sub-MIC: μg/mL grade	-	Inhibit QS-mediated biofilm formation and virulence factor production (protease, hemolysin, lipase, prodigiosin, and extracellular polysaccharide) in the uropathogen Serratia marcescens	[72]
Tyrosol/tyrosol acetate (R = H or Ac)	Oceanobacillus profundus	Caribbean soft coral Antillogorgia elisabethae	-	-	-	[49]
AHL analogs
N-(3-Hydroxydecanoyl)-l-homoserine lactone	Phaeobacter inhibens	Inner surface of an oyster shell	μM grade	Possibly by competitive inhibition of AHL-mediated QS	Inhibit virulence factor metalloprotease in Vbrio coralliilyticus	[73]
N-(Dodecanoyl-2,5-diene)-l-homoserine lactone
O-(3-Hydroxytetradecanoyl-7-ene)-l-homoserine lactone
d,l-Homocysteine thiolactone	Staphylococcus hominis	coral species (Pocillopora damicornis) in Xishan Islands, South China Sea	above 0.0625 μg/mL	Possibly compete with AHL in occupying the AHL receptor	Suppress biofilm formation and elastase production in Pseudomonas aeruginosa	[31]
Others
Honaucin A	cyanobacterium Leptolyngbya crossbyana	Corals on the Hawaiian coast	μM grade	Possibly compete with AHL in occupying the AHL receptor	-	[74]
Honaucin B				-
Honaucin C				-
Malyngolide	Cyanobacterium Lyngbya majuscula	Indian River Lagoon, USA	sub-MIC: 3.57–57 μM	Possibly inhibit QS by reducing or partially blocking the expression of lasR	Inhibit Las QS-dependent production of elastase by Pseudomonas aeruginosa, and possibly help the cyanobacterium to control growth of heterotrophic bacteria	[75]
Benzyl benzoate	Oceanobacillus sp.	Marine environment	sub-MIC: μg/mL grade	-	Inhibit pyocyanin production, elastase activity and biofilm formation of Pseudomonas aeruginosa	[65]
13Z-Octadecenal	Streptomyces griseoincarnatus	Marine sponge Callyspongia sp. from Gulf of Mannar, India	-	Bind to AHL synthase LasI of Pseudomonas aeruginosa	Possibly inhibit Pseudomonas aeruginosa biofilm	[76]

Note: MIC: minimum inhibitory concentration for microorganism growth.