Ceragenin

Class of antimicrobial compounds

Ceragenins, or cationic steroid antimicrobials (CSAs), are synthetically-produced, small-molecule chemical compounds consisting of a sterol backbone with amino acids and other chemical groups attached to them. These compounds have a net positive charge that is electrostatically attracted to the negative-charged cell membranes of certain viruses, fungi and bacteria. CSAs have a high binding affinity for such membranes (including Lipid A[1]) and are able to rapidly disrupt the target membranes leading to rapid cell death. While CSAs have a mechanism of action that is also seen in antimicrobial peptides, which form part of the body's innate immune systum, they avoid many of the difficulties associated with their use as medicines.[2]

CSA-8, member of Ceragenin family

Ceragenins were discovered by Paul B. Savage of Brigham Young University's Department of Chemistry and Biochemistry. In data previously presented by Savage and other researchers, CSAs were shown to have broad-spectrum antibacterial activity.[3] Derya Unutmaz, Associate Professor of Microbiology and Immunology at the Vanderbilt University School of Medicine, tested several CSAs in his laboratory for their ability to kill HIV directly. Unutmaz said in 2006 "We have some preliminary but very exciting results. But we would like to formally show this before making any claims that would cause unwanted hype."[4]

On February 6, 2006, researchers including Savage announced, before peer review, that a ceragenin compound, CSA-54, appeared to inactivate HIV.[2][5]

References

  1. ^ Ding B, Yin N, Liu Y, Cardenas-Garcia J, Evanson R, Orsak T, Fan M, Turin G, Savage PB (2004). "Origins of Cell Selectivity of Cationic Steroid Antibiotics". J. Am. Chem. Soc. 126 (42): 13642–13648. doi:10.1021/ja046909p. PMID 15493921.
  2. ^ a b "Vanderbilt University, Brigham Young University, and Ceragenix Pharmaceuticals Report Novel Drug Compound Kills Multiple HIV Strains; Synthetic Small Molecule Acts Through Unique Strain-Independent Virucidal Mechanism" (Press release). Ceragenix Pharmaceuticals. 2006-02-06. Archived from the original on 2006-05-23.
  3. ^ Savage PB, Li C, Taotafa U, Ding B, Guan Q (2002-11-19). "Antibacterial properties of cationic steroid antibiotics". FEMS Microbiology Letters. 217 (12): 699–704. doi:10.1111/j.1574-6968.2002.tb11448.x. PMID 5638.
  4. ^ "Chemical 'blocks HIV infection'". BBC News Online. 2006-02-09.
  5. ^ Mims, Bob (2006-02-07). "Has BYU prof found AIDS cure?". The Salt Lake Tribune. Archived from the original on 2006-04-07.

External links

  • Mitchell, Gabriel; Silvis, Melanie R.; Talkington, Kelsey C.; Budzik, Jonathan M.; Dodd, Claire E.; Paluba, Justin M.; Oki, Erika A.; Trotta, Kristine L.; Licht, Daniel J.; Jimenez-Morales, David; Chou, Seemay; Savage, Paul B.; Gross, Carol A.; Marletta, Michael A.; Cox, Jeffery S. (22 February 2022). "Ceragenins and Antimicrobial Peptides Kill Bacteria through Distinct Mechanisms". mBio. 13 (1). American Society for Microbiology: e0272621. doi:10.1128/mbio.02726-21. ISSN 2150-7511. PMC 8787472. PMID 35073755.
  • Wnorowska, Urszula; Piktel, Ewelina; Deptuła, Piotr; Wollny, Tomasz; Król, Grzegorz; Głuszek, Katarzyna; Durnaś, Bonita; Pogoda, Katarzyna; Savage, Paul B.; Bucki, Robert (10 November 2022). "Ceragenin CSA-13 displays high antibacterial efficiency in a mouse model of urinary tract infection". Scientific Reports. 12 (1): 19164. Bibcode:2022NatSR..1219164W. doi:10.1038/s41598-022-23281-y. ISSN 2045-2322. PMC 9649698. PMID 36357517.
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