Cyclodextrin derivatives as anti-infectives.

Vladimir A Karginov
Author Information
  1. Vladimir A Karginov: Innovative Biologics, Inc., 13455 Sunrise Valley Drive, Suite 200, Herndon, VA 20171, USA. Electronic address: vak@innovbio.com.

Abstract

Cyclodextrin derivatives can be utilized as anti-infectives with pore-forming proteins as the targets. The highly efficient selection of potent inhibitors was achieved because per-substituted cyclodextrins have the same symmetry as the target pores. Inhibitors of several bacterial toxins produced by Bacillus anthracis, Staphylococcus aureus, Clostridium perfringens, Clostridium botulinum, and Clostridium difficile were identified from a library of ∼200 CD derivatives. It was demonstrated that multi-targeted inhibitors can be found using this approach and could be utilized for the development of broad-spectrum drugs against various pathogens.

References

  1. Antimicrob Agents Chemother. 2008 Jun;52(6):2239-41 [PMID: 18378717]
  2. Biophys J. 2010 Jul 7;99(1):134-43 [PMID: 20655841]
  3. Antimicrob Agents Chemother. 2011 Jul;55(7):3594-7 [PMID: 21555769]
  4. Nat Rev Microbiol. 2012 Jul 02;10(8):563-74 [PMID: 22751485]
  5. Rev Physiol Biochem Pharmacol. 2004;152:183-204 [PMID: 15517462]
  6. Chem Rev. 1998 Jul 30;98(5):1743-1754 [PMID: 11848947]
  7. Front Cell Infect Microbiol. 2012 Feb 16;2:12 [PMID: 22919604]
  8. FEBS J. 2011 Dec;278(23):4602-15 [PMID: 21535407]
  9. Biophys J. 2012 Sep 19;103(6):1208-17 [PMID: 22995493]
  10. Infect Immun. 2007 Feb;75(2):1040-4 [PMID: 17101657]
  11. Chem Rev. 1998 Jul 30;98(5):2045-2076 [PMID: 11848959]
  12. Clin Microbiol Rev. 1996 Apr;9(2):216-34 [PMID: 8964036]
  13. Clin Vaccine Immunol. 2012 Mar;19(3):377-85 [PMID: 22237895]
  14. Cell Microbiol. 2012 Oct;14(10):1513-21 [PMID: 22747834]
  15. J Bacteriol. 1999 Nov;181(21):6585-90 [PMID: 10542157]
  16. Biochim Biophys Acta. 2003 Jan 10;1609(1):19-27 [PMID: 12507754]
  17. Nat Struct Mol Biol. 2004 Aug;11(8):797-8 [PMID: 15258571]
  18. Infect Immun. 1987 Dec;55(12):3103-10 [PMID: 3679545]
  19. J Biol Chem. 2002 Oct 18;277(42):39463-8 [PMID: 12177068]
  20. Toxicol Pathol. 2008 Jan;36(1):30-42 [PMID: 18337219]
  21. Lancet. 2010 May 1;375(9725):1557-68 [PMID: 20206987]
  22. Antimicrob Agents Chemother. 2010 Jan;54(1):298-304 [PMID: 19805564]
  23. Toxicon. 2001 Nov;39(11):1661-72 [PMID: 11595629]
  24. Curr Opin Biotechnol. 2000 Dec;11(6):625-36 [PMID: 11102800]
  25. Bioorg Med Chem. 2007 Aug 15;15(16):5424-31 [PMID: 17572091]
  26. Expert Opin Biol Ther. 2007 Jun;7(6):843-54 [PMID: 17555370]
  27. EMBO J. 1985 Nov;4(11):3021-4 [PMID: 4065098]
  28. Antimicrob Agents Chemother. 2007 Jan;51(1):245-51 [PMID: 17074791]
  29. Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18453-8 [PMID: 23100532]
  30. Int J Nanomedicine. 2011;6:3173-86 [PMID: 22228990]
  31. N Engl J Med. 1998 Aug 20;339(8):520-32 [PMID: 9709046]
  32. Mol Aspects Med. 2009 Dec;30(6):439-55 [PMID: 19638283]
  33. Annu Rev Biochem. 2007;76:243-65 [PMID: 17335404]
  34. Biomacromolecules. 2011 Mar 14;12(3):791-6 [PMID: 21302959]
  35. Bioorg Med Chem. 2006 Jan 1;14(1):33-40 [PMID: 16169738]
  36. J Infect Dis. 2010 Oct 1;202(7):1050-8 [PMID: 20726702]
  37. Nat Rev Microbiol. 2009 Sep;7(9):629-41 [PMID: 19680247]
  38. Antimicrob Agents Chemother. 2006 Nov;50(11):3740-53 [PMID: 16982795]
  39. Cell. 1985 Mar;40(3):627-33 [PMID: 3882238]
  40. Future Microbiol. 2009 Feb;4(1):35-43 [PMID: 19207098]
  41. J Exp Med. 2008 Feb 18;205(2):287-94 [PMID: 18268041]
  42. J Mol Biol. 2009 Sep 25;392(3):614-29 [PMID: 19627991]
  43. J Pharm Pharmacol. 2010 Nov;62(11):1607-21 [PMID: 21039545]
  44. Science. 1996 Dec 13;274(5294):1859-66 [PMID: 8943190]
  45. Chem Rev. 1998 Jul 30;98(5):1977-1996 [PMID: 11848955]
  46. Proc Natl Acad Sci U S A. 2005 Oct 18;102(42):15075-80 [PMID: 16214885]
  47. ChemMedChem. 2011 Jan 3;6(1):181-92 [PMID: 21140396]
  48. J Pharm Biomed Anal. 2008 Jul 15;47(3):535-40 [PMID: 18367363]
  49. PLoS One. 2011;6(8):e23927 [PMID: 21887348]
  50. Science. 2005 Jul 29;309(5735):777-81 [PMID: 16051798]
  51. Cell Host Microbe. 2012 Sep 13;12(3):266-75 [PMID: 22980324]

Grants

  1. R43 AI074105/NIAID NIH HHS
  2. R43 AI052894/NIAID NIH HHS
  3. R44 AI052894/NIAID NIH HHS
  4. R44 AI074105/NIAID NIH HHS
  5. R43 AI082749/NIAID NIH HHS

MeSH Term

Animals
Anti-Bacterial Agents
Bacillus anthracis
Bacterial Toxins
Clostridium perfringens
Cyclodextrins
Humans
Staphylococcus aureus

Chemicals

Anti-Bacterial Agents
Bacterial Toxins
Cyclodextrins

Word Cloud

Created with Highcharts 10.0.0derivativesClostridiumCyclodextrincanutilizedanti-infectivesinhibitorspore-formingproteinstargetshighlyefficientselectionpotentachievedper-substitutedcyclodextrinssymmetrytargetporesInhibitorsseveralbacterialtoxinsproducedBacillusanthracisStaphylococcusaureusperfringensbotulinumdifficileidentifiedlibrary∼200CDdemonstratedmulti-targetedfoundusingapproachdevelopmentbroad-spectrumdrugsvariouspathogens

Similar Articles

Cited By