Journal of the American Oil Chemists' Society

, Volume 90, Issue 3, pp 437–448 | Cite as

Chemo-Enzymatic Synthesis and Antimicrobial Evaluation of Alkyloxy Propanol Amine-Based Cationic Ether Lipids

  • J. R. C. Reddy
  • B. V. S. K. Rao
  • M. S. L. Karuna
  • K. P. Kumar
  • U. S. N. Murthy
  • R. B. N. Prasad
Original Paper


The present study involved the synthesis and antimicrobial evaluation of alkyloxy propanol amine-based cationic lipids N,N-dimethyl-1-octadecylamino-3-alkyloxy-2-propanol (series A, 7a–e) and N-methyl-N,N-di-(2-hydroxy-3-alkyloxy-2 propyl) octadecylamine (series B, 9a–e) and their acetylated derivatives (8a–e and 10a–e). A simple three-step chemo-enzymatic approach was employed for the synthesis of 7a–e and 9a–e in 71–80 and 67–88 % yields, respectively. The first step involved the synthesis of a series of glycidyl ethers from a series of alcohols (C4, C8, C10, C12, C14) which were opened in the second step with octadecylamine to obtain 1-octadecylamino-3-alkyloxy-2 propanol (5a–e) and N,N-di-(2-hydroxy-3-alkyloxypropyl) octadecylamine (6a–e). In the third step, alkyloxy propanolamines (5a–e, 6a–e) were quaternized using methyl iodide to yield quaternized ammonium salts. The quaternized ammonium salts were enzymatically acetylated using Candida antarctica lipase-B based immobilized enzyme Novozym 435 to obtain their acetylated derivatives. The quaternized salts as well as their acetylated derivatives were evaluated for antibacterial and antifungal properties. The title compounds were found to possess moderate to good antibacterial activities against all the studied bacterial strains namely, Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Klebsiella aerogenes compared to streptomycin and cetyl trimethyl ammonium bromide (CTAB). The title compounds exhibited relatively good antifungal activities against Candida albicans and no significant activities against other fungal strains namely, Saccharomyces cerevisiae, Rhizopus oryzae and Aspergillus niger when compared to amphotericin B and CTAB.


Antimicrobial activity Cationic-ether lipids Chemo-enzymatic synthesis Quaternized salts Alkyloxy-propanolamine 


  1. 1.
    Mauleon D, Dolors PM, Rosell G (1988) β-Adrenergic antagonists: N-alkyl and N-amidoethyl(aryloxy) propanolamines related to propanolol. Eur J Med Chem 23:421–426CrossRefGoogle Scholar
  2. 2.
    Macchia B, Balsamo A, Lapucci A, Machia F, Martinelli A, Ammon HL, Prasad SM, Breschi MC, Ducci M, Martonotti E (1987) Role of the (acyloxy) methyl moiety in eliciting the adrenergic β-blocking activity of 3-(acyloxy) propanol amines. J Med Chem 30:616–622CrossRefGoogle Scholar
  3. 3.
    Reinehr D, Topfl R (1993) Phenyl alkyl glycidyl ether addition products. US Patent 5(250):202Google Scholar
  4. 4.
    Barlow JJ, Smith LH (1991) Alkanolamine derivatives. US Patent 4(550):111Google Scholar
  5. 5.
    Kim TS, Hirao T, Ikeda I (1996) Preparation of bis-quaternary ammonium salts from epichlorohydrin. J Am Oil Chem Soc 73:67–71CrossRefGoogle Scholar
  6. 6.
    Satge’de Caro P, Mouloungui Z, Gaset A (1997) Synthesis of alkyloxy (di)alkylamino propanols, hydroxy alkyloxy (di)alkyloxyamino propanols, and the dimer compounds for use as fuel additives. J Am Oil Chem Soc 74:235–240CrossRefGoogle Scholar
  7. 7.
    Mangold HK (1988) Ether lipids: relic of the past and promise for the future. Riv Ital Sostanze Grasse 65:349–360Google Scholar
  8. 8.
    Demopoulos CA, Pickard RN, Hanahan DJ (1979) Platelet activating factor: evidence for 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine as the active component (A new class of lipid chemical mediators). J Biol Chem 254:9355–9358Google Scholar
  9. 9.
    Miller AD (1998) Cationic liposomes for gene therapy. Angew Chem Int Ed Engl 37:1768–1785CrossRefGoogle Scholar
  10. 10.
    Deshmukh HM, Huang L (1997) Liposome and polylysine mediated gene transfer. New J Chem 21:113–124Google Scholar
  11. 11.
    Behr JP (1993) Synthetic gene transfer vectors. Acc Chem Res 26:274–278CrossRefGoogle Scholar
  12. 12.
    Bhattacharya S, Mandal SS (1998) Evidence of interlipidic ion-pairing in anion-induced DNA release from cationic amphiphile; DNA complexes, mechanistic implications in transfection. Biochemistry 37:7764–7777CrossRefGoogle Scholar
  13. 13.
    Carmona-Ribeiro AM, Vieira DB, Nilton L (2006) Cationic surfactants and lipids as anti-infective agents. Anti Infect Agents Med Chem 5:33–54CrossRefGoogle Scholar
  14. 14.
    Vieira DB, Carmona-Ribeiro AM (2006) Cationic lipids and surfactants as antifungal agents: mode of action. J Anti microb Chemother 58:760–767CrossRefGoogle Scholar
  15. 15.
    Priyanka J, Anand ON (2001) Alkyloxy alkylamino propanols as multifunctional fuel stabilizers. Petrol Sci Technol 19:411–424CrossRefGoogle Scholar
  16. 16.
    Karuna MSL, Devi BLAP, Prasad PSS, Prasad RBN (2009) Synthesis of sulfated sodium salts of 1-alkylamino-3 alkyloxy-2-propanols and N,N-di-(2-hydroxy-3-alkyloxy propyl) alkylamines as potential surfactants. J Surfact Deterg 12:117–123CrossRefGoogle Scholar
  17. 17.
    National committee for clinical laboratory standards approved standards (NCCLS): M2-A6 (1997) Performance standards for antimicrobial disk susceptibility testing. NCCLS (6th edn)Google Scholar
  18. 18.
    Linday EM (1962) Practical introduction to microbiology. E. & F.N. Spon, London, p 178Google Scholar
  19. 19.
    Yumi O, Yukishige K, Kazuo K, Toshi T, Norio Y (2008) Synthesis and antibacterial activity of quaternary ammonium salt-type antibacterial agents with a phosphate group. J Oleo Sci 57:445–452CrossRefGoogle Scholar
  20. 20.
    Sun JY, Li J, Qiu XL, Quing FL (2005) Synthesis and structure-activity relationship (SAR) of novel perfluoroalkyl-containing quaternary ammonium salts. J Fluorine Chem 126:1425–1431CrossRefGoogle Scholar
  21. 21.
    Banno T, Toshima K, Kawada K, Matsumura S (2007) Synthesis and properties of biodegradable and chemically recyclable cationic surfactants containing carbonate linkages. J Oleo Sci 56:493–499CrossRefGoogle Scholar
  22. 22.
    Kabara JJ (ed) (1990) Science of antisepsis and bactericidal agent p 20Google Scholar

Copyright information

© AOCS 2012

Authors and Affiliations

  • J. R. C. Reddy
    • 1
  • B. V. S. K. Rao
    • 1
  • M. S. L. Karuna
    • 1
  • K. P. Kumar
    • 2
  • U. S. N. Murthy
    • 2
  • R. B. N. Prasad
    • 1
  1. 1.Centre for Lipid ResearchIndian Institute of Chemical TechnologyHyderabadIndia
  2. 2.Biology DivisionIndian Institute of Chemical TechnologyHyderabadIndia

Personalised recommendations