Aminoalkylcarbamoylphosphonates reduce TNFα release from activated immune cells

Efrat Harel, Abraham Rubinstein, Weibin Chen, Eli Breuer*, Boaz Tirosh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Some carbamoylphosphonates (CPOs) inhibit matrix metalloproteinases (MMPs). Although MMPs are involved in inflammatory processes, the anti-inflammatory activity of CPOs has not been reported. In this context we compared the biological activity of the three aminoCPOs, PYR-CPO, PIP-CPO and cis-ACCP. We were particularly interested in their capability to modulate the secretion of tumor necrosis factor alpha (TNFα). LPS-activated mouse peritoneal macrophages and LPS-activated mouse splenocytes were used to explore this question. It was found that the aminoCPOs were able to reduce TNFα secretion to a level equivalent to the reduction caused by the steroid drug budesonide (BUD). The reduction in TNFα levels was neither accompanied by cytotoxicity, nor did it inhibit cell proliferation. To explicate whether the aminoCPOs affect TNFα processing by TNFα-converting enzyme (TACE), TACE inhibitory properties of the three molecules was tested in vitro. Only PIP-CPO exerted TACE inhibitory activity at therapeutic (non-cytotoxic) concentrations, indicating on its potential to serve as an anti-inflammatory agent by reducing TNFα secretion.

Original languageAmerican English
Pages (from-to)6518-6523
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Issue number22
StatePublished - 15 Nov 2010

Bibliographical note

Funding Information:
The skillful assistance of Mrs. Rivka Hadar is greatly acknowledged. This work was supported in part by the Ministry of Science of Israel, in part by The German Israeli Foundation for Scientific Research and Development (GIF), and in part by the Grass Center for Drug Design and Synthesis of Novel Therapeutics to EB AR, BT and EB are affiliated with the David R. Bloom Center of Pharmacy, in the School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem. BT is affiliated with the Dr. Adolf and Klara Brettler Centre for Research in Molecular Pharmacology and Therapeutics at the Hebrew University.


  • Carbamoylphosphonate
  • Inflammation
  • Matrix metalloproteinase inhibitor
  • Phosphonate
  • TACE
  • TNFα


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