Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/33859
- Modified norcantharidins: synthesis, protein phosphatases 1 and 2A inhibition, and anticancer activity
Hart, Matthew E.;
Chamberlin, A. Richard;
Sakoff, Jennette A.;
- The University of Newcastle. Faculty of Science & Information Technology, School of Environmental and Life Science
- Fourteen modified norcantharidin analogues have been synthesised and screened for their ability to inhibit the serine/threonine protein phosphatases 1 and 2A. The most potent compounds found were 10 (PP1 IC₅₀=13±5 μM; PP2A IC₅₀=7±3 μM) and 16 (PP1 IC₅₀=18±8 μM; PP2A IC₅₀=3.2±0.4 μM). Overall, only analogues possessing at least one acidic residue at the former anhydride warhead displayed any PP1 or PP2A inhibitory action. The ability of these analogues to inhibit PP1 and PP2A correlates well with their observed anti-cancer activity against a panel of five cancer cell lines: A2780 (human ovarian carcinoma), G401 (human kidney carcinoma), HT29 (human colorectal carcinoma), H460 (human lung carcinoma) and L1210 (murine leukemia).
- Bioorganic & Medicinal Chemistry Letters Vol. 14, Issue 8, p. 1969-1973
- Publisher Link
- Elsevier Ltd.
serine/threonine protein phosphatases;
- Resource Type
- journal article