Synthesis, modelling and kinetic assays of potent inhibitors of purple acid phosphatase

Mohd-Pahmi, Siti Hajar, Hussein, Waleed M., Schenk, Gerhard and McGeary, Ross P. (2011) Synthesis, modelling and kinetic assays of potent inhibitors of purple acid phosphatase. Bioorganic and Medicinal Chemistry Letters, 21 10: 3092-3094. doi:10.1016/j.bmcl.2011.03.024


Author Mohd-Pahmi, Siti Hajar
Hussein, Waleed M.
Schenk, Gerhard
McGeary, Ross P.
Title Synthesis, modelling and kinetic assays of potent inhibitors of purple acid phosphatase
Journal name Bioorganic and Medicinal Chemistry Letters   Check publisher's open access policy
ISSN 0960-894X
1464-3405
Publication date 2011-05-15
Sub-type Article (original research)
DOI 10.1016/j.bmcl.2011.03.024
Volume 21
Issue 10
Start page 3092
End page 3094
Total pages 3
Place of publication Oxford, United Kingdom
Publisher Pergamon
Collection year 2012
Language eng
Formatted abstract
Purple acid phosphatases (PAPs) are binuclear metallohydrolases that have been isolated from various mammals, plants, fungi and bacteria. In mammals PAP activity is associated with bone resorption and can lead to bone metabolic disorders such as osteoporosis; thus human PAP is an attractive target to develop anti-osteoporotic drugs. Based on a previous lead compound and rational drug design, acyl derivatives of α-aminonaphthylmethylphosphonic acid were synthesised and tested as PAP inhibitors. Kinetic analysis showed that they are good PAP inhibitors whose potencies improve with increasing acyl chain length. Maximum potency is reached when the number of carbons in the acyl chain is between 12 and 14. The most potent inhibitor of red kidney bean PAP is the dodecyl-derivative with Kic = 5 μM, while the most potent pig PAP inhibitor is the tetradecyl-derivative with Kic = 8 μM, the most potent inhibitor of a mammalian PAP yet reported.
Keyword Purple acid phosphatase
PAP
Phosphonate
Osteoporosis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Chemistry and Molecular Biosciences
School of Pharmacy Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 10 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 10 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Thu, 28 Jul 2011, 12:22:41 EST by Charna Kovacevic on behalf of School of Chemistry & Molecular Biosciences