Medicinal Chemistry Research

, Volume 26, Issue 10, pp 2592–2601 | Cite as

Synthesis, characterization, antimicrobial and anti-biofilm activity of a new class of 11-bromoundecanoic acid-based betaines

  • Sathyam Reddy Yasa
  • Y. Poornachandra
  • C. Ganesh Kumar
  • Vijayalakshmi Penumarthy
Original Research
  • 91 Downloads

Abstract

Novel betaines were synthesized from esterquats, which in turn were obtained from the reaction of 11-bromo undecanoic acid, different alkyl amines, and methyl iodide. The synthesized betaines were characterized by fourier transform infrared, proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, and mass spectral analysis. These betaines were synthesized in four steps; in the first step, 11-bromo undecanoic acid was converted into methyl 11-bromoundecanoate followed by the synthesis of secondary amine monoester, and tertiary amine mono and diesters by the reaction of 11-bromoundecanoate with different aliphatic amines (hexyl, dodecyl, octadecyl, dioctyl, and dicyclohexyl amine). In the third step, the prepared secondary amine monoesters, tertiary amine mono, and diesters were converted into monoesterquats and diesterquats by reacting with methyl iodide. The resultant esterquats were converted into betaines by saponification reaction using LiOH.H2O in water and tetrahydrofuran. The synthesized compounds (5ah) were studied for their antimicrobial activity. Some of the compounds showed good to moderate antibacterial activity with minimum inhibitory concentration values ranging between 3.9–31.2 µg mL−1 and antifungal activity with minimum inhibitory concentration values ranging between 7.8–62.4 µg mL−1. Further, some of the betaines also showed good anti-biofilm activity with IC50 values ranging between 2.1–25.3 µg mL−1 on the tested pathogenic microbial and fungal strains.

Keywords

11-Bromoundecanoic acid Esterquats Betaines Antimicrobial activity Anti-biofilm activity 

Notes

Acknowledgements

One of the authors Sathyam Reddy gratefully acknowledges the Department of Biotechnology (DBT), New Delhi for the financial assistance under sponsored project and the Director, CSIR-IICT for providing the facilities.

Supplementary material

44_2017_1958_MOESM1_ESM.doc (546 kb)
Supplementary Information

References

  1. Abdel-Ghany YS, Ihnat MA, Miller DD, Kunin CM, Tong HH (1993) Structure-activity relationship of glycine betaine analogues on osmotolerance of enteric bacteria. J Med Chem 36:784–789CrossRefPubMedGoogle Scholar
  2. Amin US, Lash TD, Wilkinson BJ (1995) Proline betaine is a highly effective osmoprotectant for Staphylococcus aureus. Arch Microbiol 163:138–142CrossRefPubMedGoogle Scholar
  3. Amsterdam D (1996) Susceptibility testing of antimicrobials in liquid media. In: Loman V (ed) Antibiotics in laboratory medicine, 4th edn. Williams and Wilkins, Baltimore, MD, p 52–111Google Scholar
  4. Baaman RA (1978) Anti-plaque agents. US Patent 4130637Google Scholar
  5. Birnie CR, Malamud D, Schnaare RL (2000) Antimicrobial evaluation of N-alkyl betaines and N-Alkyl-N,N-dimethylamine oxides with variations in chain length. Antimicrob Agents Chemother 44:2514–2517CrossRefPubMedPubMedCentralGoogle Scholar
  6. Cosquer A, Ficamos M, Jebbar M, Corbel JC, Choquet G, Fontenelle C, Uriac P, Bernard T (2004) Antibacterial activity of glycine betaine analogues: involvement of osmoporters. Bioorg Med Chem Lett 14:2061–2065CrossRefPubMedGoogle Scholar
  7. Davies D (2003) Understanding biofilm resistance to antibacterial agents. Nat Rev Drug Disc 2:114–122CrossRefGoogle Scholar
  8. Dixon SJ, Stockwell BR (2013) The role of iron and reactive oxygen species in cell death. Nat Chem Biol 10:9–17CrossRefGoogle Scholar
  9. Domingo X (1990) Betaines. In: Lomax EG (ed) Amphoteric Surfactants. Marcel Dekker, New York, NY, p 76–190Google Scholar
  10. Godzisz D, Ilczyszyn MM, Ilczyszyn M (2002) Classification and nature of hydrogen bonds to betaine. X-ray, 13C CP MAS and IR description of low barrier hydrogen bonds. J Mol Struct 606:123–137CrossRefGoogle Scholar
  11. Halliwell B, Aruoma OI (1991) DNA damage by oxygen-derived species. Its mechanism and measurement in mammalian systems. FEBS Lett 281:9–19CrossRefPubMedGoogle Scholar
  12. Jennings MC, Minbiole KP, Wuest WM (2015) Quaternary ammonium compounds: An antimicrobial mainstay and platform for innovation to address bacterial resistance. ACS Infect Dis 1:288–303CrossRefPubMedGoogle Scholar
  13. Kobayashi D, Kondo K, Uehara N, Otokozawa S, Tsuji N, Yagihashi A, Watanabe N (2002) Endogenous reactive oxygen species is an important mediator of miconazole antifungal effect. Antimicrob Agents Chemother 46:3113–3117CrossRefPubMedPubMedCentralGoogle Scholar
  14. Kowalczyk I (2008) Synthesis, molecular structure and spectral properties of quaternary ammonium derivatives of 1,1-dimethyl-1,3-propylenediamine. Molecules 13:379–390CrossRefPubMedGoogle Scholar
  15. Kumar CG, Poornachandra Y (2015) Biodirected synthesis of miconazole-conjugated bacterial silver nanoparticles and their applications as antifungal agents and drug delivery vehicles. Colloids Surf B Biointerfaces 125:110–119CrossRefPubMedGoogle Scholar
  16. Kumar R, Kalur GC, Ziserman L, Danino D, Raghavan SR (2007) Wormlike micelles of a C22-tailed zwitterionic betaine surfactant: from viscoelastic solutions to elastic gels. Langmuir 23:12849–12856CrossRefPubMedGoogle Scholar
  17. Lindstedt M, Allenmark S, Thompson RA, Edebo L (1990) Antimicrobial activity of betaine esters, quaternary ammonium amphiphiles which spontaneously hydrolyze into nontoxic components. Antimicrob Agents Chemother 34:1949–1954CrossRefPubMedPubMedCentralGoogle Scholar
  18. Madeo F, Frohlich E, Ligr M, Grey M, Sigrist SJ, Wolf DH, Frohlich KU (1999) Oxygen stress: a regulator of apoptosis in yeast. J Cell Biol 145:757–767CrossRefPubMedPubMedCentralGoogle Scholar
  19. Olson I (2015) Biofilm-specific antibiotic tolerance and resistance. Eur J Clin Microbiol Infect Dis 34:877–886CrossRefGoogle Scholar
  20. Peddie BA, Wood JE, Lever M, Happer DA, de Zwart F, Chambers ST (2003) Assessment of antimicrobial activity of hydrophilic betaines in osmotically stressed bacteria. Antonie Van Leeuwenhoek 83:175–181CrossRefPubMedGoogle Scholar
  21. Quan H, Zhang X, Lu H, Huang Z (2012) Synthesis and acid solution properties of a novel betaine zwitterionic surfactant. Cent Eur J Chem 10:1624–1632Google Scholar
  22. Robert J, Ferlauto Jr, Yuhasz KM (1988) Stable antiplaque dentifrice. US Patent 4774077Google Scholar
  23. Schaack G (1990) Experimental results on phase transitions in betaine compounds. Ferroelectrics 104:147–158CrossRefGoogle Scholar
  24. Srinivas R, Garu A, Moku G, Agawane SB, Chaudhuri A (2012) A long-lasting dendritic cell DNA vaccination system using lysinylated amphiphiles with mannose-mimicking head-groups. Biomaterials 33:6220–6229CrossRefPubMedGoogle Scholar
  25. Yasa SR, Kaki SS, Poornachandra Y, Kumar CG, Penumarthy V (2016) Synthesis, characterization, antimicrobial and biofilm inhibitory studies of new esterquats. Bioorg Med Chem Lett 26:1978–1982CrossRefPubMedGoogle Scholar
  26. Zhou M, Huang Z, Yu S, Yang Y, Huang Y, Qiu D, Zhao J (2016) Synthesis and surface active properties of novel oligomer betaine surfactants. Tenside Surfactants Deterg 53:134–139CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Sathyam Reddy Yasa
    • 1
  • Y. Poornachandra
    • 2
  • C. Ganesh Kumar
    • 2
  • Vijayalakshmi Penumarthy
    • 1
  1. 1.Centre for Lipid ResearchCSIR-Indian Institute of Chemical TechnologyHyderabadIndia
  2. 2.Medicinal Chemistry and Pharmacology DivisionCSIR-Indian Institute of Chemical TechnologyHyderabadIndia

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