Abstract
The widespread use of antibiotics has led to an increase in the number of strains resistant to major antibacterial pharmaceuticals. Many synthesized quaternary ammonium compounds possess antibacterial, antifungal and antiviral properties. Incorporation of quaternary ammonium moieties into dendrimers represents a promising strategy for the preparation of novel antimicrobial biomaterials. Here, poly(quaternary ammonium) chloride dendrimers were synthesized by functionalizing poly(propylene imine) (PPI) dendrimer with various lengths of alkyl chains. In vitro antimicrobial assays indicate that the amphiphilic dendrimers are potent antimicrobial agents with activity against multidrug-resistant pathogens such as the methicillin-resistant Staphylococcus aureus.
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Abd-Elzaher MM, Ali IAI (2006) Preparation, characterization and biological studies of some novel ferrocenyl compounds. Appl Organomet Chem 20(2):107–111. https://doi.org/10.1002/aoc.1016
Bourne N, Stanberry LR, Kern ER, Holan G, Matthews B, Bernstein DI (2000) Dendrimers, a new class of candidate topical microbicides with activity against herpes simplex virus infection. Antimicrob Agents Chemother 44(9):2471–2474. https://doi.org/10.1128/AAC.44.9.2471-2474.2000
Breukink E, Wiedemann I, Cv Kraaij, Kuipers OP, Sahl H-G, de Kruijff B (1999) Use of the cell wall precursor lipid II by a pore-forming peptide antibiotic. Science 286(5448):2361–2364. https://doi.org/10.1126/science.286.5448.2361
Chen CZ, Cooper SL (2000) Recent advances in antimicrobial dendrimers. Adv Mater 12(11):843–846. https://doi.org/10.1002/(sici)1521-4095(200006)12:11<843::aid-adma843>3.0.co;2-t
Chen CZ, Cooper SL (2002) Interactions between dendrimer biocides and bacterial membranes. Biomaterials 23(16):3359–3368. https://doi.org/10.1016/S0142-9612(02)00036-4
Chen CZ, Cooper SL, Tan NCB (1999) Incorporation of dimethyldodecylammonium chloride functionalities onto poly(propylene imine) dendrimers significantly enhances their antibacterial properties. Chem Commun 16:1585–1586. https://doi.org/10.1039/a904662c
Chen CZ, Beck-Tan NC, Dhurjati P, van Dyk TK, LaRossa RA, Cooper SL (2000) Quaternary ammonium functionalized poly(propylene imine) dendrimers as effective antimicrobials: structure–activity studies. Biomacromolecules 1(3):473–480. https://doi.org/10.1021/bm0055495
Chen MY et al (2009) A randomized controlled trial of the safety of candidate microbicide SPL7013 gel when applied to the penis. J Acquir Immune Defic Syndr 50(4):375–380. https://doi.org/10.1097/QAI.0b013e318198a7e6
de Queiroz AAA et al (2006) Physicochemical and antimicrobial properties of boron-complexed polyglycerol–chitosan dendrimers. J Biomater Sci Polym Ed 17(6):689–707. https://doi.org/10.1163/156856206777346313
Denyer SP (1995) Mechanisms of action of antibacterial biocides. Int Biodeterior Biodegradation 36(3):227–245. https://doi.org/10.1016/0964-8305(96)00015-7
Hong S et al (2004) Interaction of poly(amidoamine) dendrimers with supported lipid bilayers and cells: hole formation and the relation to transport. Bioconjug Chem 15(4):774–782. https://doi.org/10.1021/bc049962b
Kawabata N, Nishiguchi M (1988) Antibacterial activity of soluble pyridinium-type polymers. Appl Environ Microbiol 54(10):2532–2535
Kenawy el R, Worley SD, Broughton R (2007) The chemistry and applications of antimicrobial polymers: a state-of-the-art review. Biomacromolecules 8(5):1359–1384. https://doi.org/10.1021/bm061150q
Klajnert B, Janiszewska J, Urbanczyk-Lipkowska Z, Bryszewska M, Shcharbin D, Labieniec M (2006) Biological properties of low molecular mass peptide dendrimers. Int J Pharm 309(1–2):208–217. https://doi.org/10.1016/j.ijpharm.2005.10.039
Mecke A et al (2004) Direct observation of lipid bilayer disruption by poly(amidoamine) dendrimers. Chem Phys Lipids 132(1):3–14. https://doi.org/10.1016/j.chemphyslip.2004.09.001
Meyers SR, Juhn FS, Griset AP, Luman NR, Grinstaff MW (2008) Anionic amphiphilic dendrimers as antibacterial agents. J Am Chem Soc 130(44):14444–14445. https://doi.org/10.1021/ja806912a
Murugan E, Pakrudheen I (2012) New amphiphilic poly(quaternary ammonium) dendrimer catalyst for effective reduction of citronellal. Appl Catal A Gen 439–440:142–148. https://doi.org/10.1016/j.apcata.2012.06.053
O’Loughlin J, Millwood IY, McDonald HM, Price CF, Kaldor JM, Paull JRA (2010) Safety, tolerability, and pharmacokinetics of SPL7013 gel (VivaGel®): a dose ranging, phase I study. Sex Transm Dis 37(2):100–104. https://doi.org/10.1097/OLQ.0b013e3181bc0aac
Palermo EF, Kuroda K (2009) Chemical structure of cationic groups in amphiphilic polymethacrylates modulates the antimicrobial and hemolytic activities. Biomacromolecules 10(6):1416–1428. https://doi.org/10.1021/bm900044x
Palermo EF, Sovadinova I, Kuroda K (2009) Structural determinants of antimicrobial activity and biocompatibility in membrane-disrupting methacrylamide random copolymers. Biomacromolecules 10(11):3098–3107. https://doi.org/10.1021/bm900784x
Piantavigna S, McCubbin GA, Boehnke S, Graham B, Spiccia L, Martin LL (2011) A mechanistic investigation of cell-penetrating Tat peptides with supported lipid membranes. Biochim Biophys Acta Biomembr 1808(7):1811–1817. https://doi.org/10.1016/j.bbamem.2011.03.002
Rojo J, Delgado R (2004) Glycodendritic structures: promising new antiviral drugs. J Antimicrob Chemother 54(3):579–581. https://doi.org/10.1093/jac/dkh399
Simoncic B, Tomsic B (2010) Structures of novel antimicrobial agents for textiles—a review. Text Res J 80(14):1721–1737. https://doi.org/10.1177/0040517510363193
Stratton TR, Howarter JA, Allison BC, Applegate BM, Youngblood JP (2010) Structure–activity relationships of antibacterial and biocompatible copolymers. Biomacromolecules 11(5):1286–1290. https://doi.org/10.1021/bm1000839
Sun B, Slomberg DL, Chudasama SL, Lu Y, Schoenfisch MH (2012) Nitric oxide-releasing dendrimers as antibacterial agents. Biomacromolecules 13(10):3343–3354. https://doi.org/10.1021/bm301109c
Tashiro T (2001) Antibacterial and bacterium adsorbing macromolecules. Macromol Mater Eng 286(2):63–87. https://doi.org/10.1002/1439-2054(20010201)286:2<63::aid-mame63>3.0.co;2-h
Thorsteinsson T, Másson M, Kristinsson KG, Hjálmarsdóttir MA, Hilmarsson H, Loftsson T (2003) Soft antimicrobial agents: synthesis and activity of labile environmentally friendly long chain quaternary ammonium compounds. J Med Chem 46(19):4173–4181. https://doi.org/10.1021/jm030829z
Timofeeva LM, Kleshcheva NA, Moroz AF, Didenko LV (2009) Secondary and tertiary polydiallylammonium salts: novel polymers with high antimicrobial activity. Biomacromolecules 10(11):2976–2986. https://doi.org/10.1021/bm900435v
Tulu M, Aghatabay NM, Senel M, Dizman C, Parali T, Dulger B (2009) Synthesis, characterization and antimicrobial activity of water soluble dendritic macromolecules. Eur J Med Chem 44(3):1093–1099. https://doi.org/10.1016/j.ejmech.2008.06.016
Waschinski CJ et al (2008) Insights in the antibacterial action of poly(methyloxazoline)s with a biocidal end group and varying satellite groups. Biomacromolecules 9(7):1764–1771. https://doi.org/10.1021/bm7013944
Westman E-H, Ek M, Enarsson L-E, Wågberg L (2009) Assessment of antibacterial properties of polyvinylamine (PVAm) with different charge densities and hydrophobic modifications. Biomacromolecules 10(6):1478–1483. https://doi.org/10.1021/bm900088r
Worley BV, Slomberg DL, Schoenfisch MH (2014) Nitric oxide-releasing quaternary ammonium-modified poly(amidoamine) dendrimers as dual action antibacterial agents. Bioconjug Chem 25(5):918–927. https://doi.org/10.1021/bc5000719
Wu LP, Ficker M, Christensen JB, Trohopoulos PN, Moghimi SM (2015) Dendrimers in medicine: therapeutic concepts and pharmaceutical challenges. Bioconjug Chem 26(7):1198–1211. https://doi.org/10.1021/acs.bioconjchem.5b00031
Yang L, Wang X, Suchyta DJ, Schoenfisch MH (2018) Antibacterial activity of nitric oxide-releasing hyperbranched polyamidoamines. Bioconjug Chem 29(1):35–43. https://doi.org/10.1021/acs.bioconjchem.7b00537
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Pakrudheen, I., Banu, A.N. & Murugan, E. Cationic amphiphilic dendrimers with tunable hydrophobicity show in vitro activity. Environ Chem Lett 16, 1513–1519 (2018). https://doi.org/10.1007/s10311-018-0769-9
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DOI: https://doi.org/10.1007/s10311-018-0769-9