Abstract
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.
References
Mauleon D, Dolors PM, Rosell G (1988) β-Adrenergic antagonists: N-alkyl and N-amidoethyl(aryloxy) propanolamines related to propanolol. Eur J Med Chem 23:421–426
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 30:616–622
Reinehr D, Topfl R (1993) Phenyl alkyl glycidyl ether addition products. US Patent 5(250):202
Barlow JJ, Smith LH (1991) Alkanolamine derivatives. US Patent 4(550):111
Kim TS, Hirao T, Ikeda I (1996) Preparation of bis-quaternary ammonium salts from epichlorohydrin. J Am Oil Chem Soc 73:67–71
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 74:235–240
Mangold HK (1988) Ether lipids: relic of the past and promise for the future. Riv Ital Sostanze Grasse 65:349–360
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 254:9355–9358
Miller AD (1998) Cationic liposomes for gene therapy. Angew Chem Int Ed Engl 37:1768–1785
Deshmukh HM, Huang L (1997) Liposome and polylysine mediated gene transfer. New J Chem 21:113–124
Behr JP (1993) Synthetic gene transfer vectors. Acc Chem Res 26:274–278
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 37:7764–7777
Carmona-Ribeiro AM, Vieira DB, Nilton L (2006) Cationic surfactants and lipids as anti-infective agents. Anti Infect Agents Med Chem 5:33–54
Vieira DB, Carmona-Ribeiro AM (2006) Cationic lipids and surfactants as antifungal agents: mode of action. J Anti microb Chemother 58:760–767
Priyanka J, Anand ON (2001) Alkyloxy alkylamino propanols as multifunctional fuel stabilizers. Petrol Sci Technol 19:411–424
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 12:117–123
National committee for clinical laboratory standards approved standards (NCCLS): M2-A6 (1997) Performance standards for antimicrobial disk susceptibility testing. NCCLS (6th edn)
Linday EM (1962) Practical introduction to microbiology. E. & F.N. Spon, London, p 178
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 57:445–452
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 126:1425–1431
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 56:493–499
Kabara JJ (ed) (1990) Science of antisepsis and bactericidal agent p 20
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Reddy, J.R.C., Rao, B.V.S.K., Karuna, M.S.L. et al. Chemo-Enzymatic Synthesis and Antimicrobial Evaluation of Alkyloxy Propanol Amine-Based Cationic Ether Lipids. J Am Oil Chem Soc 90, 437–448 (2013). https://doi.org/10.1007/s11746-012-2177-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11746-012-2177-9