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Cationic Lipoaminoacid Derivatives of Diethanolamine As Potentially Membrane-Active Antibacterial Agents

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Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

This work is aimed to develop several cationic amphiphiles based on amino acid derivatives of diethanolamine as potentially membrane-active antibacterial agents. The developed compounds contain two amino acid residues in the polar block and aliphatic chains of various length in the hydrophobic domain. Amphiphiles were obtained in preparative amounts sufficient to confirm their structures and perform a study of antibacterial activity. The synthesized samples based on β-Ala (4c) and GABA (4d) with aliphatic C12 chain in the hydrophobic domain showed a promising level of antimicrobial activity against gram-positive (B. subtilis) and gram-negative (E. coli) bacteria (minimal inhibitory concentration, MIC, 1 μg/mL). Amphiphiles containing aromatic amino acids L-Phe (6a) and L-Trp (6b) in the polar head group and C8 hydrocarbon chain exhibited an antibacterial activity against B. subtilis with MIC of 1 μg/mL. The obtained data on antimicrobial activity make the selected compounds attractive for further detailed study of their mechanism of action.

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REFERENCES

  1. Yount N.Y., Yeaman M.R. 2004. Multidimensional signatures in antimicrobial peptides. Proc. Natl. Acad. Sci. USA. 101 (19), 7363. https://doi.org/10.1073/pnas.0401567101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Musin K.G. 2018. Antimicrobial peptides—a potential replacement for traditional antibiotics. Rus. J. Infection and Immunity. 8 (3), 295–308. https://doi.org/10.15789/2220-7619-2018-3-295-308

    Article  Google Scholar 

  3. Rima M., Rima M., Fajloun Z., Sabatier J.-M., Bechinger B., Naas T. 2021. Antimicrobial peptides: A potent alternative to antibiotics. Antibiotics. 10 (9), 1095. https://doi.org/10.3390/antibiotics10091095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Molchanova N., Hansen P.R., Franzyk H. 2017. Advances in development of antimicrobial peptidomimetics as hotential drugs. Molecules. 22 (9), 1430. https://doi.org/10.3390/molecules22091430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Pirri G., Giuliani A., Nicoletto S.F., Pizzuto L., Rinaldi A.C. 2009. Lipopeptides as anti-infectives: A practical perspective. Cent. Eur. J. Biol. 4(3), 258–273. https://doi.org/10.2478/s11535-009-0031-3

    Article  CAS  Google Scholar 

  6. Fjell C.D., Hiss J.A., Hancock R.E. W., Schneider G. 2012. Designing antimicrobial peptides: Form follows function. Nat. Rev. Drug Discovery. 11, 37–51.

    Article  CAS  Google Scholar 

  7. Faber C., Stallmann H., Lyaruu D., Joosten U., Von Eiff C., van Nieuw Amerongen A., Wuisman P.I. 2005. Comparable efficacies of the antimicrobial peptide human lactoferrin 1-11 and gentamicin in a chronic methicillin-resistant Staphylococcus aureus osteomyelitis model. Antimicrob. Agents Chemother. 49 (6), 2438–2444. https://doi.org/10.1128/AAC.49.6.2438-2444.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lin L., Chi J., Yan Y., Luo R., Feng X., Zheng Y., Xian D., Li X., Quan G., Liu D, Wu C., Lu C., Pan X. 2021. Membrane-disruptive peptides/peptidomimetics-based therapeutics: Promising systems to combat bacteria and cancer in the drug-resistant era. Acta Pharm. Sin B. 11 (9), 2609. https://doi.org/10.1016/j.apsb.2021.07.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Tague A.J., Putsathit P., Hammer K.A., Wales S.M., Knight D.R., Riley T.V., Keller P.A., Pyne S.G. 2019. Cationic biaryl 1,2,3-triazolyl peptidomimetic amphiphiles: Synthesis, antibacterial evaluation and preliminary mechanism of action studies. Eur. J. Med. Chem. 168, 386. https://doi.org/10.1016/j.ejmech.2019.02.013

    Article  CAS  PubMed  Google Scholar 

  10. Mojsoska B., Jenssen H. 2015. Peptides and peptidomimetics for antimicrobial drug design. Pharmaceuticals (Basel). 8(3), 366–415. https://doi.org/10.3390/ph8030366

    Article  CAS  PubMed  Google Scholar 

  11. Zhang E., Bai P.-Y., Cui D.-Y., Chu W.-C., Hua Y.-G., Liu Q., Yin H.-Y., Zhang Y.-J., Qin S., Liu H.-M. 2018. Synthesis and bioactivities study of new antibacterial peptide mimics: The dialkyl cationic amphiphiles. Europ. J. Med. Chem. 143, 1489–1509. https://doi.org/10.1016/j.ejmech.2017.10.044

    Article  CAS  Google Scholar 

  12. Su M., Xia D., Teng P., Nimmagadda A., Zhang C., Odom T., Cao A., Hu Y., Cai J. 2017. Membrane-active hydantoin derivatives as antibiotic agents. J. Med. Chem. 60 (20), 8456. https://doi.org/10.1021/acs.jmedchem.7b00847

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Konai M.M., Ghosh C., Yarlagadda V. 2014. Membrane active phenylalanine conjugated lipophilic norspermidine derivatives with selective antibacterial activity. J. Med. Chem. 57, 9409–9423. https://doi.org/10.1021/jm5013566

    Article  CAS  PubMed  Google Scholar 

  14. Ghosh C., Sarkar P., Samaddar S., Uppua D., Haldar J. 2017. L-Lysine based lipidated biphenyls as agents with anti-biofilm and anti-inflammatory properties that also inhibit intracellular bacteria. Chem. Commun. 53, 8427–8430. https://doi.org/10.1039/C7CC04206J

    Article  CAS  Google Scholar 

  15. Lohan S., Kalanta A., Sonkusre P., Cameotra S. S., Bisht G. S. 2014. Development of novel membrane active lipidated peptidomimetics active against drug resistant clinical isolates. Bioorg. & Med. Chem. 22, 4544–4552. https://doi.org/10.1016/j.bmc.2014.07.041

    Article  CAS  Google Scholar 

  16. Schnaider L., Brahmachari S., Schmidt N.W., Mensa B., Shaham-Niv S., Bychenko D., Adler-Abramovich L., Shimon L.J.W., Kolusheva S., DeGrado W.F., Gazit E. 2017. Self-assembling dipeptide antibacterial nanostructures with membrane disrupting activity. Nat. Commun. 8 (1), 1365. https://doi.org/10.1038/s41467-017-01447-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Shahane G., Ding W., Palaiokostas M., Azevedo H.S., Orsi M. 2019. Interaction of antimicrobial lipopeptides with bacterial lipid bilayers. J. Membr. Biol. 252 (4–5). 317. https://doi.org/10.1007/s00232-019-00068-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yar M., Mushtaq N., Afzal S. 2013. Synthesis, reactions, applications, and biological activity of diethanolamine and its derivatives. Russ. J. Org. Chem. 49 (7) 949–967. https://doi.org/10.1134/S1070428013070014

    Article  CAS  Google Scholar 

  19. Denieva Z.G., Romanova N.A., Bodrova T.G., Budanova U.A., Sebyakin Yu.L. 2019. Synthesis of amphiphilic peptidomimetics based on the aliphatic derivatives of natural amino acids. Moscow Univ. Chem. Bull. 74 (6), 300–305. https://doi.org/10.3103/S0027131419060087

    Article  Google Scholar 

  20. Makovitzki A., Baram J., Shai Y. 2008. Antimicrobial lipopolypeptides composed of palmitoyl Di- and tricationic peptides: In vitro and in vivo activities, self-assembly to nanostructures, and a plausible mode of action. Biochemistry. 47 (40), 10630. https://doi.org/10.1021/bi8011675

    Article  CAS  PubMed  Google Scholar 

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Funding

The work was supported by the Russian Foundation for Basic Research (project no. 20-04-00672). The work was performed using the equipment of the Center for Collective Use of MIREA – Russian technology university supported by the RF Ministry of Education and Science (Agreement no. 075-15-2021-689 dated September 1, 2021).

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Authors and Affiliations

  1. MIREA, Russian Technology University, Lomonosov Institute of Fine Chemical Technology, 119571, Moscow, Russia

    M. K. Guseva, U. A. Budanova & Yu. L. Sebyakin

  2. Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, 119071, Moscow, Russia

    Z. G. Denieva

Authors
  1. M. K. Guseva
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  2. Z. G. Denieva
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  3. U. A. Budanova
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  4. Yu. L. Sebyakin
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Correspondence to U. A. Budanova.

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The authors declare that they have no conflict of interest.

This article does not contain any studies involving animals or human participants performed by any of the authors.

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Translated by A. Dunina-Barkovskaya

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Guseva, M.K., Denieva, Z.G., Budanova, U.A. et al. Cationic Lipoaminoacid Derivatives of Diethanolamine As Potentially Membrane-Active Antibacterial Agents. Biochem. Moscow Suppl. Ser. A 17, 148–155 (2023). https://doi.org/10.1134/S1990747823020034

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  • DOI: https://doi.org/10.1134/S1990747823020034

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