4 butyrolactone


Summary: One of the FURANS with a carbonyl thereby forming a cyclic lactone. It is an endogenous compound made from gamma-aminobutyrate and is the precursor of gamma-hydroxybutyrate. It is also used as a pharmacological agent and solvent.

Top Publications

  1. Kuang X, Du J, Chen Y, Wang J, Wang Y. Protective effect of Z-ligustilide against amyloid beta-induced neurotoxicity is associated with decreased pro-inflammatory markers in rat brains. Pharmacol Biochem Behav. 2009;92:635-41 pubmed publisher
    ..LIG would be a potential candidate for further preclinical study aimed at the prevention and treatment of cognitive deficits in AD. ..
  2. Geske G, O Neill J, Blackwell H. Expanding dialogues: from natural autoinducers to non-natural analogues that modulate quorum sensing in Gram-negative bacteria. Chem Soc Rev. 2008;37:1432-47 pubmed publisher
  3. Swem L, Swem D, Wingreen N, Bassler B. Deducing receptor signaling parameters from in vivo analysis: LuxN/AI-1 quorum sensing in Vibrio harveyi. Cell. 2008;134:461-73 pubmed publisher
    ..We find that quorum-sensing-mediated communication can be manipulated positively and negatively to control bacterial behavior and, more broadly, that signaling parameters can be deduced from in vivo data. ..
  4. von Rad U, Klein I, Dobrev P, Kottova J, Zazimalova E, Fekete A, et al. Response of Arabidopsis thaliana to N-hexanoyl-DL-homoserine-lactone, a bacterial quorum sensing molecule produced in the rhizosphere. Planta. 2008;229:73-85 pubmed publisher
    ..In sum, the bacterial quorum sensing signal C6-HSL does induce transcriptional changes in Arabidopsis and may contribute to tuning plant growth to the microbial composition of the rhizosphere...
  5. Yu Y, Du J, Wang C, Qian Z. Protection against hydrogen peroxide-induced injury by Z-ligustilide in PC12 cells. Exp Brain Res. 2008;184:307-12 pubmed
    ..These findings suggest that Z-LIG may be useful in the treatment of neurodegenerative disorders in which oxidative stress and apoptosis are mainly implicated. ..
  6. Kuang X, Du J, Liu Y, Zhang G, Peng H. Postischemic administration of Z-Ligustilide ameliorates cognitive dysfunction and brain damage induced by permanent forebrain ischemia in rats. Pharmacol Biochem Behav. 2008;88:213-21 pubmed
    ..The present findings suggest that LIG may have therapeutic potential in treating vascular dementia and cerebrovascular insufficiency. ..
  7. Dekimpe V, Déziel E. Revisiting the quorum-sensing hierarchy in Pseudomonas aeruginosa: the transcriptional regulator RhlR regulates LasR-specific factors. Microbiology. 2009;155:712-23 pubmed publisher
    ..This work demonstrates that the QS hierarchy is more complex than the model simply presenting the las system above the rhl system. ..
  8. Zhang X, Kundoor V, Khalifa S, Zeman D, Fahmy H, Dwivedi C. Chemopreventive effects of sarcophine-diol on skin tumor development in CD-1 mice. Cancer Lett. 2007;253:53-9 pubmed
    ..SD resulted in a 95% reduction in 12-O-tetradecanoylphorbol-13-acetate-induced DNA synthesis. SD could be an effective chemopreventive agent for skin cancer by enhancing apoptosis and decreasing cell proliferation. ..
  9. Bignell D, Bate N, Cundliffe E. Regulation of tylosin production: role of a TylP-interactive ligand. Mol Microbiol. 2007;63:838-47 pubmed
    ..Continued synthesis of tylosin by the disrupted strains contrasts with other reports that loss of gamma-butyrolactones abolishes antibiotic production. ..

More Information


  1. Schuhegger R, Ihring A, Gantner S, Bahnweg G, Knappe C, Vogg G, et al. Induction of systemic resistance in tomato by N-acyl-L-homoserine lactone-producing rhizosphere bacteria. Plant Cell Environ. 2006;29:909-18 pubmed
    ..e. PR1a, 26 kDa acidic and 30 kDa basic chitinase). Together, these data support the view that AHL molecules play a role in the biocontrol activity of rhizobacteria through the induction of systemic resistance to pathogens...
  2. Sjöblom S, Brader G, Koch G, Palva E. Cooperation of two distinct ExpR regulators controls quorum sensing specificity and virulence in the plant pathogen Erwinia carotovora. Mol Microbiol. 2006;60:1474-89 pubmed
    ..These results suggest that Ecc is able to react both to the cognate AHSL signal and the signals produced by other bacterial species. ..
  3. Du J, Bai B, Kuang X, Yu Y, Wang C, Ke Y, et al. Ligustilide inhibits spontaneous and agonists- or K+ depolarization-induced contraction of rat uterus. J Ethnopharmacol. 2006;108:54-8 pubmed
    ..The data also imply strongly that LIG is one of active ingredients of Danggui and has the potential to be developed into an effective drug for the prevention and treatment of primary dysmenorrhoea. ..
  4. Takano E. Gamma-butyrolactones: Streptomyces signalling molecules regulating antibiotic production and differentiation. Curr Opin Microbiol. 2006;9:287-94 pubmed
    ..The importance of understanding how secondary metabolites are regulated and how environmental and physiological signals are sensed highlights the relevance of studying this system. ..
  5. Nealson K, Hastings J. Quorum sensing on a global scale: massive numbers of bioluminescent bacteria make milky seas. Appl Environ Microbiol. 2006;72:2295-7 pubmed
  6. D Angelo Picard C, Faure D, Penot I, Dessaux Y. Diversity of N-acyl homoserine lactone-producing and -degrading bacteria in soil and tobacco rhizosphere. Environ Microbiol. 2005;7:1796-808 pubmed
  7. Hsiao N, Söding J, Linke D, Lange C, Hertweck C, Wohlleben W, et al. ScbA from Streptomyces coelicolor A3(2) has homology to fatty acid synthases and is able to synthesize gamma-butyrolactones. Microbiology. 2007;153:1394-404 pubmed
  8. Reading N, Sperandio V. Quorum sensing: the many languages of bacteria. FEMS Microbiol Lett. 2006;254:1-11 pubmed
    ..Three major quorum-sensing circuits have been described: one used primarily by Gram-negative bacteria, one used primarily by Gram-positive bacteria, and one that has been proposed to be universal. ..
  9. Van Houdt R, Aertsen A, Moons P, Vanoirbeek K, Michiels C. N-acyl-L-homoserine lactone signal interception by Escherichia coli. FEMS Microbiol Lett. 2006;256:83-9 pubmed
    ..In conclusion, our work shows that E. coli has the capacity to alter its pattern of gene expression and its phenotypical properties in response to AHLs by means of the AHL responsive transcriptional regulator SdiA. ..
  10. Kuang X, Yao Y, Du J, Liu Y, Wang C, Qian Z. Neuroprotective role of Z-ligustilide against forebrain ischemic injury in ICR mice. Brain Res. 2006;1102:145-53 pubmed
    ..The antioxidant and anti-apoptotic properties of LIG may contribute to the neuroprotective potential of LIG in cerebral ischemic damage. ..
  11. Sawant S, Youssef D, Mayer A, Sylvester P, Wali V, Arant M, et al. Anticancer and anti-inflammatory sulfur-containing semisynthetic derivatives of sarcophine. Chem Pharm Bull (Tokyo). 2006;54:1119-23 pubmed
    ..The effect of these derivatives on highly malignant +SA mammary epithialial cell proliferation is reported. Anti-inflammatory potential of sarcophine and its derivatives is also demonstrated. ..
  12. Muller J, Kuttler C, Hense B, Rothballer M, Hartmann A. Cell-cell communication by quorum sensing and dimension-reduction. J Math Biol. 2006;53:672-702 pubmed
    ..Concluding, we apply the modeling approach to spatially structured experimental data. ..
  13. Cai L, Marshall T, Uetrecht A, Schafer D, Bear J. Coronin 1B coordinates Arp2/3 complex and cofilin activities at the leading edge. Cell. 2007;128:915-29 pubmed
    ..We conclude that Coronin 1B's coordination of filament formation by Arp2/3 complex and filament turnover by Cofilin is required for effective lamellipodial protrusion and cell migration. ..
  14. Eberl L. Quorum sensing in the genus Burkholderia. Int J Med Microbiol. 2006;296:103-10 pubmed
    ..Given the essential role of QS in the expression of pathogenic traits in Burkholderia these regulatory systems represent attractive targets for the development of novel therapeutics. ..
  15. Scott R, Weil J, Le P, Williams P, Fray R, von Bodman S, et al. Long- and short-chain plant-produced bacterial N-acyl-homoserine lactones become components of phyllosphere, rhizosphere, and soil. Mol Plant Microbe Interact. 2006;19:227-39 pubmed
    ..Therefore, it is feasible to use bioengineered plants to supplement soils with specific acyl-HSLs to modulate bacterial phenotypes and plant-associated bacterial community structures. ..
  16. Peng H, Du J, Zhang G, Kuang X, Liu Y, Qian Z, et al. Neuroprotective effect of Z-ligustilide against permanent focal ischemic damage in rats. Biol Pharm Bull. 2007;30:309-12 pubmed
  17. Kato J, Funa N, Watanabe H, Ohnishi Y, Horinouchi S. Biosynthesis of gamma-butyrolactone autoregulators that switch on secondary metabolism and morphological development in Streptomyces. Proc Natl Acad Sci U S A. 2007;104:2378-83 pubmed
    ..AfsA is thus the key enzyme for the biosynthesis of gamma-butyrolactones. ..
  18. Du J, Yu Y, Ke Y, Wang C, Zhu L, Qian Z. Ligustilide attenuates pain behavior induced by acetic acid or formalin. J Ethnopharmacol. 2007;112:211-4 pubmed
  19. Aydogmus Z, Topcu G, Güven K. Studies on chemical constituents of Gracilaria verrucosa. Nat Prod Res. 2008;22:1589-96 pubmed publisher
    ..6%) in addition to a few hydrocarbons, simple aromatics and a new compound, namely 3,4-dimethyl-5-carboxyclic acid-1-oxacyclopent-3-en-2-one. The structures of the isolated compounds have been elucidated by spectroscopic methods. ..
  20. Ammar S, Edziri H, Mahjoub M, Chatter R, Bouraoui A, Mighri Z. Spasmolytic and anti-inflammatory effects of constituents from Hertia cheirifolia. Phytomedicine. 2009;16:1156-61 pubmed publisher
    ..screening of the crude extracts showed spasmolytic and anti-inflammatory positive results. The antispasmodic effect of Bakkenolide was found in the same range as that of Alverine, a standard musculotropic spasmolytic agent. ..
  21. Ferreira E, Vireque A, Adona P, Ferriani R, Navarro P. Prematuration of bovine oocytes with butyrolactone I reversibly arrests meiosis without increasing meiotic abnormalities after in vitro maturation. Eur J Obstet Gynecol Reprod Biol. 2009;145:76-80 pubmed publisher
    ..8% for the control, BLI 18h and BLI 24h, respectively). Prematuration with butyrolactone I reversibly arrests meiosis without damaging the meiotic spindle or the chromosome distribution of bovine oocytes after in vitro maturation. ..
  22. Oliver C, Schaefer A, Greenberg E, Sufrin J. Microwave synthesis and evaluation of phenacylhomoserine lactones as anticancer compounds that minimally activate quorum sensing pathways in Pseudomonas aeruginosa. J Med Chem. 2009;52:1569-75 pubmed publisher
    ..Compound 12b, 3-oxo-12-phenyldodecanoyl-L-homoserine lactone, was identified as a lead compound with strong cancer growth inhibitory activity that minimizes activation of QS signaling pathways in a P. aeruginosa reporter assay. ..
  23. Michel J, Chen Y, Zhang H, Huang Y, Krunic A, Orjala J, et al. Estrogenic and serotonergic butenolides from the leaves of Piper hispidum Swingle (Piperaceae). J Ethnopharmacol. 2010;129:220-6 pubmed publisher
    ..Extracts of Piper hispidum Swingle (Piperaceae), bound to the estrogen (ER) and serotonin (5-HT7) receptors...
  24. Xie J, Lu J, Qian Z, Yu Y, Duan J, Li S. Optimization and comparison of five methods for extraction of coniferyl ferulate from Angelica sinensis. Molecules. 2009;14:555-65 pubmed publisher
    ..It was noteworthy that the content of ligustilide and coniferyl ferulate was not detectable in the decoction, the commonly used oral administration form of Traditional Chinese Medicines in clinical practice. ..
  25. Balde E, Andolfi A, Bruyère C, Cimmino A, Lamoral Theys D, Vurro M, et al. Investigations of fungal secondary metabolites with potential anticancer activity. J Nat Prod. 2010;73:969-71 pubmed publisher
    ..The preliminary results from the current study have stimulated further structure-activity investigations with respect to the growth inhibitory activity of compounds belonging to the bisorbicillinoid group. ..
  26. Birmele M, Ripp S, Jegier P, Roberts M, Sayler G, Garland J. Characterization and validation of a bioluminescent bioreporter for the direct detection of Escherichia coli. J Microbiol Methods. 2008;75:354-6 pubmed publisher
  27. Wojtowicz J, Yarema M, Wax P. Withdrawal from gamma-hydroxybutyrate, 1,4-butanediol and gamma-butyrolactone: a case report and systematic review. CJEM. 2008;10:69-74 pubmed
    ..Emergency physicians must consider withdrawal from these agents when patients present with clinical features suggestive of a sedative-hypnotic withdrawal syndrome. ..
  28. Kaufmann G, Park J, Janda K. Bacterial quorum sensing: a new target for anti-infective immunotherapy. Expert Opin Biol Ther. 2008;8:719-24 pubmed
    ..aeruginosa and S. aureus and their QS systems as targets for intervention. New research strongly suggests that QS systems represent attractive targets for discovery of novel anti-infective agents, including immunotherapeutic strategies. ..
  29. Lupu R, Colomer R, Menendez J. An easy, rapid and objective mathematical method to identify fatty acid synthase (oncogenic antigen-519) modulators with potential anticancer value. Clin Transl Oncol. 2008;10:219-26 pubmed
    ..This "C75-sensitivity test" might offer an easy, rapid and objective method to identify FASN inhibitors with potential anticancer value in human cancer. ..
  30. Su S, Khan S, Farrand S. Induction and loss of Ti plasmid conjugative competence in response to the acyl-homoserine lactone quorum-sensing signal. J Bacteriol. 2008;190:4398-407 pubmed publisher
  31. Kuo S, Hsieh T, Wang Y, Lo W, Hsui Y, Chen C. Cytotoxic constituents from the leaves of Cinnamomum subavenium. Chem Pharm Bull (Tokyo). 2008;56:97-101 pubmed
    ..Propidium iodide staining and cytometry analysis were used to evaluate the cell cycle progression of the treated SW480 cells and it was found that 1 and 2 caused DNA damage in a dose- and time-dependent manner. ..
  32. Hawkins A, Arnold F, Stuermer R, Hauer B, Leadbetter J. Directed evolution of Vibrio fischeri LuxR for improved response to butanoyl-homoserine lactone. Appl Environ Microbiol. 2007;73:5775-81 pubmed
    ..These data confirm that LuxR is evolutionarily pliable and suggest that LuxR is not intrinsically asymmetric in its response to quorum-sensing signals with different acyl-side-chain lengths. ..
  33. Cailleau T, Cooke J, Davies S, Ling K, Naylor A, Nicholson R, et al. Asymmetric synthesis of beta-amino-gamma-substituted-gamma-butyrolactones: double diastereoselective conjugate addition of homochiral lithium amides to homochiral alpha,beta-unsaturated esters. Org Biomol Chem. 2007;5:3922-31 pubmed
    ..Subsequent O-deprotection and cyclisation of the resultant beta-amino adducts gives access to the corresponding beta-amino-gamma-substituted-gamma-butyrolactones in good yield and high de. ..
  34. Bachmeier B, Mirisola V, Romeo F, Generoso L, Esposito A, Dell eva R, et al. Reference profile correlation reveals estrogen-like trancriptional activity of Curcumin. Cell Physiol Biochem. 2010;26:471-82 pubmed publisher
    ..This approach demonstrates estrogenic effects of putative phytoestrogens at physiological concentrations and shows, for the first time, estrogenic effects of Curcumin. ..
  35. Duerkop B, Herman J, Ulrich R, Churchill M, Greenberg E. The Burkholderia mallei BmaR3-BmaI3 quorum-sensing system produces and responds to N-3-hydroxy-octanoyl homoserine lactone. J Bacteriol. 2008;190:5137-41 pubmed publisher
    ..In recombinant E. coli, BmaR3 responds to 3OHC8-HSL but not to other acyl-HSLs. These data indicate that the signal for BmaR3-BmaI3 quorum sensing is 3OHC8-HSL. ..
  36. Constantoulakis P, Filiou E, Rovina N, Chras G, Hamhougia A, Karabela S, et al. In vivo expression of innate immunity markers in patients with Mycobacterium tuberculosis infection. BMC Infect Dis. 2010;10:243 pubmed publisher
    ..However, further studies are needed, in order to elucidate whether the selective upregulation of these factors in the infected patients could serve as a specific molecular marker of tuberculosis. ..
  37. Kajikawa T, Aoki K, Iwashita T, Niedzwiedzki D, Frank H, Katsumura S. Syntheses of ylidenbutenolide-modified derivatives of peridinin and their stereochemical and spectral characteristics. Org Biomol Chem. 2010;8:2513-6 pubmed publisher
  38. Miura D, Saarinen N, Miura Y, Santti R, Yagasaki K. Hydroxymatairesinol and its mammalian metabolite enterolactone reduce the growth and metastasis of subcutaneous AH109A hepatomas in rats. Nutr Cancer. 2007;58:49-59 pubmed
    ..These in vitro and in vivo findings suggest that HMR has inhibitory activities on tumor growth and metastasis in the hepatoma-bearing rats, and that this anti-tumor effect is mediated at least partially by ENL, a metabolite of HMR. ..
  39. Smyth A, Cifelli P, Ortori C, Righetti K, Lewis S, Erskine P, et al. Garlic as an inhibitor of Pseudomonas aeruginosa quorum sensing in cystic fibrosis--a pilot randomized controlled trial. Pediatr Pulmonol. 2010;45:356-62 pubmed publisher
    ..Garlic capsules were well tolerated. Although there was no significant effect of garlic compared to placebo in this pilot study, there was a suggestion of improvement with garlic which should be investigated in a larger trial. ..
  40. Kitson R, Taylor R, Wood J. A one-pot, base-free annelation approach to alpha-alkylidene-gamma-butyrolactones. Org Lett. 2009;11:5338-41 pubmed publisher
    ..The procedure is "base-free" and is useful for the preparation of a range of alpha-alkylidene-gamma-butyrolactones including alpha-methylene-gamma-butyrolactone examples, which can be particularly base-sensitive. ..
  41. Praneenararat T, Geske G, Blackwell H. Efficient synthesis and evaluation of quorum-sensing modulators using small molecule macroarrays. Org Lett. 2009;11:4600-3 pubmed publisher
    ..Several QS antagonists were discovered and serve to showcase the macroarray as a straightforward technique for QS research. ..
  42. Lin L, Zhao Q, Li A, Ren F, Yang F, Wang R. Enantioselective synthesis of Anomala osakana pheromone and Janus integer pheromone: a flexible approach to chiral gamma-butyrolactones. Org Biomol Chem. 2009;7:3663-5 pubmed publisher
  43. Imperio D, Pirali T, Galli U, Pagliai F, Cafici L, Canonico P, et al. Replacement of the lactone moiety on podophyllotoxin and steganacin analogues with a 1,5-disubstituted 1,2,3-triazole via ruthenium-catalyzed click chemistry. Bioorg Med Chem. 2007;15:6748-57 pubmed
    ..The present structures might therefore represent a good platform for the fast generation of metabolically stable compounds with few stereogenic centers that might be of value from a medicinal chemistry point of view. ..
  44. Adlercreutz H. Lignans and human health. Crit Rev Clin Lab Sci. 2007;44:483-525 pubmed
    ..The source of the lignans seems to play a role because other factors in the food obviously participate in the protective effects. The results are promising, but much work is still needed in this area of medicine. ..
  45. Williams P. Quorum sensing, communication and cross-kingdom signalling in the bacterial world. Microbiology. 2007;153:3923-38 pubmed
  46. Vial L, Groleau M, Dekimpe V, Déziel E. Burkholderia diversity and versatility: an inventory of the extracellular products. J Microbiol Biotechnol. 2007;17:1407-29 pubmed
    ..Available information on regulation, especially quorum sensing mechanisms, and secretion is highlighted. ..
  47. Yang X, Zhu J, Tang C, Ke C, Lin G, Cheng T, et al. Alkaloids from roots of Stemona sessilifolia and their antitussive activities. Planta Med. 2009;75:174-7 pubmed publisher
    ..c. v. administration. ..
  48. Clemen C, Rybakin V, Eichinger L. The coronin family of proteins. Subcell Biochem. 2008;48:1-5 pubmed publisher
    ..The book should be of interest for scientists outside the field, but is more importantly intended as a fast and competent guide for newcomers as well as doctoral and postdoctoral scientists to coronin research in all its facets. ..
  49. Dai W, Shi J. Diversity-oriented synthesis and solid-phase organic synthesis under controlled microwave heating. Comb Chem High Throughput Screen. 2007;10:837-56 pubmed
    ..A traceless synthesis of indole sulfonamides via microwave-assisted Cu(II)-catalyzed heteroannulation of the catlinker-tethered substrates is also given. ..
  50. Papadakis E, Lazarou D, Grougnet R, Magiatis P, Skaltsounis A, Papadopoulou Mourkidou E, et al. Effect of the form of the sesame-based diet on the absorption of lignans. Br J Nutr. 2008;100:1213-9 pubmed publisher
    ..Overall, the levels of the sesame lignans and enterolignans present in plasma seem to be influenced not only by the amount of lignan intake but also by other factors such as the form of the sesame-based diet. ..
  51. Ramachary D, Vijayendar Reddy Y. A general approach to chiral building blocks via direct amino acid-catalyzed cascade three-component reductive alkylations: formal total synthesis of HIV-1 protease inhibitors, antibiotic agglomerins, brefeldin A, and (R)-gamma-hexanolide. J Org Chem. 2010;75:74-85 pubmed publisher
    ..In this context, many of the pharmaceutically applicable chiral building blocks were prepared via MCC reactions. ..
  52. Dowling G, Gallo P, Regan L. Confirmatory analysis of firocoxib in bovine milk by rapid resolution liquid chromatography tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2009;877:541-6 pubmed publisher
    ..The precision of the method, expressed as RSD values for the within-lab reproducibility at the three levels of fortification (5, 7.5 and 10ng/mL) was less than 11% respectively. ..
  53. Bayindir U, Alfermann A, Fuss E. Hinokinin biosynthesis in Linum corymbulosum Reichenb. Plant J. 2008;55:810-20 pubmed publisher
    ..Our results strongly indicate that PLR-Lc1 participates in (-)-hinokinin biosynthesis in L. corymbulosum by the first of the two hypothetical pathways via (-)-secoisolariciresinol. ..