Skip to main content

Antibacterial activity of berberine-NorA pump inhibitor hybrids with a methylene ether linking group

Journal Article


Abstract


  • Reduced and carboxymethylated-κ-casein (RCM-κ-CN) is a milk-derived amyloidogenic protein that readily undergoes nucleation-dependent aggregation and amyloid fibril formation via a similar pathway to disease-specific amyloidogenic peptides like amyloid beta (Aβ), which is associated with Alzheimer’s disease. In this study, a series of flavonoids, many known to be inhibitors of Aβ fibril formation, were screened for their ability to inhibit RCM-κ-CN fibrilisation, and the results were compared with literature data on Aβ inhibition. Flavonoids that had a high degree of hydroxylation and molecular planarity gave good inhibition of RCM-κ-CN fibril formation. IC50 values were between 10- and 200-fold higher with RCM-κ-CN than literature results for Aβ fibril inhibition, however, with few exceptions, they showed a similar trend in potency. The convenience and reproducibility of the RCM-κ-CN assay make it an economic alternative first screen for Aβ inhibitory activity, especially for use with large compound libraries.

Authors


  •   Samosorn, Siritrin (external author)
  •   Tanwirat, Bongkot (external author)
  •   Muhamad, Nussara (external author)
  •   Casadei, Gabriele (external author)
  •   Tomkiewicz, Danuta (external author)
  •   Lewis, Kim (external author)
  •   Suksamrarn, Apichart (external author)
  •   Prammananan, Therdsak (external author)
  •   Gornall, Karina (external author)
  •   Beck, Jennifer L.
  •   Bremner, John B.

Publication Date


  • 2009

Citation


  • Samosorn, S., Tanwirat, B., Muhamad, N., Casadei, G., Tomkiewicz, D., Lewis, K., Suksamrarn, A., Prammananan, T., Gornall, K. C., Beck, J. L. & Bremner, J. B. (2009). Antibacterial activity of berberine-NorA pump inhibitor hybrids with a methylene ether linking group. Bioorganic & Medicinal Chemistry, 17 (11), 3866-3872.

Scopus Eid


  • 2-s2.0-65549100031

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/4973

Number Of Pages


  • 6

Start Page


  • 3866

End Page


  • 3872

Volume


  • 17

Issue


  • 11

Place Of Publication


  • http://www.elsevier.com/wps/find/journaldescription.cws_home/129/description#description

Abstract


  • Reduced and carboxymethylated-κ-casein (RCM-κ-CN) is a milk-derived amyloidogenic protein that readily undergoes nucleation-dependent aggregation and amyloid fibril formation via a similar pathway to disease-specific amyloidogenic peptides like amyloid beta (Aβ), which is associated with Alzheimer’s disease. In this study, a series of flavonoids, many known to be inhibitors of Aβ fibril formation, were screened for their ability to inhibit RCM-κ-CN fibrilisation, and the results were compared with literature data on Aβ inhibition. Flavonoids that had a high degree of hydroxylation and molecular planarity gave good inhibition of RCM-κ-CN fibril formation. IC50 values were between 10- and 200-fold higher with RCM-κ-CN than literature results for Aβ fibril inhibition, however, with few exceptions, they showed a similar trend in potency. The convenience and reproducibility of the RCM-κ-CN assay make it an economic alternative first screen for Aβ inhibitory activity, especially for use with large compound libraries.

Authors


  •   Samosorn, Siritrin (external author)
  •   Tanwirat, Bongkot (external author)
  •   Muhamad, Nussara (external author)
  •   Casadei, Gabriele (external author)
  •   Tomkiewicz, Danuta (external author)
  •   Lewis, Kim (external author)
  •   Suksamrarn, Apichart (external author)
  •   Prammananan, Therdsak (external author)
  •   Gornall, Karina (external author)
  •   Beck, Jennifer L.
  •   Bremner, John B.

Publication Date


  • 2009

Citation


  • Samosorn, S., Tanwirat, B., Muhamad, N., Casadei, G., Tomkiewicz, D., Lewis, K., Suksamrarn, A., Prammananan, T., Gornall, K. C., Beck, J. L. & Bremner, J. B. (2009). Antibacterial activity of berberine-NorA pump inhibitor hybrids with a methylene ether linking group. Bioorganic & Medicinal Chemistry, 17 (11), 3866-3872.

Scopus Eid


  • 2-s2.0-65549100031

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/4973

Number Of Pages


  • 6

Start Page


  • 3866

End Page


  • 3872

Volume


  • 17

Issue


  • 11

Place Of Publication


  • http://www.elsevier.com/wps/find/journaldescription.cws_home/129/description#description