Abstract
2-(Acyloxy)ethylphosphonate analogues of geranyl, farnesyl, and geranylgeranyl pyrophosphate have been prepared. Horner-Wadsworth-Emmons condensation of different terpene aldehydes with an unsymmetrical bisphosphonate was the key step in syntheses of the phosphonates bearing α,β-unsaturated acyloxy groups. After preparation of the respective phosphonic acids through reaction with TMSBr, both acids and esters were tested for their effects on DNA synthesis in human-derived myeloid and lymphoid leukemia cell lines. The phosphonate esters varied substantially in their ability to impair proliferation of the different cell lines, but testing against one possible target, farnesyl protein transferase (FPTase), revealed little impact at concentrations ranging up to 10μM. Because the corresponding 2,3-dihydro compounds showed similar biological activity, conjugate addition would not appear to be involved in the toxicity. Copyright (C) 2000 Elsevier Science Ltd.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2729-2737 |
| Number of pages | 9 |
| Journal | Bioorganic and Medicinal Chemistry |
| Volume | 8 |
| Issue number | 12 |
| DOIs | |
| State | Published - Nov 27 2000 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry
Cite this
}
2-(Acyloxy)ethylphosphonate analogues of prenyl pyrophosphates : synthesis and biological characterization. / Cermak, Diana M.; Wiemer, David F.; Lewis, Kriste; Hohl, Raymond.
In: Bioorganic and Medicinal Chemistry, Vol. 8, No. 12, 27.11.2000, p. 2729-2737.Research output: Contribution to journal › Article
TY - JOUR
T1 - 2-(Acyloxy)ethylphosphonate analogues of prenyl pyrophosphates
T2 - synthesis and biological characterization
AU - Cermak, Diana M.
AU - Wiemer, David F.
AU - Lewis, Kriste
AU - Hohl, Raymond
PY - 2000/11/27
Y1 - 2000/11/27
N2 - 2-(Acyloxy)ethylphosphonate analogues of geranyl, farnesyl, and geranylgeranyl pyrophosphate have been prepared. Horner-Wadsworth-Emmons condensation of different terpene aldehydes with an unsymmetrical bisphosphonate was the key step in syntheses of the phosphonates bearing α,β-unsaturated acyloxy groups. After preparation of the respective phosphonic acids through reaction with TMSBr, both acids and esters were tested for their effects on DNA synthesis in human-derived myeloid and lymphoid leukemia cell lines. The phosphonate esters varied substantially in their ability to impair proliferation of the different cell lines, but testing against one possible target, farnesyl protein transferase (FPTase), revealed little impact at concentrations ranging up to 10μM. Because the corresponding 2,3-dihydro compounds showed similar biological activity, conjugate addition would not appear to be involved in the toxicity. Copyright (C) 2000 Elsevier Science Ltd.
AB - 2-(Acyloxy)ethylphosphonate analogues of geranyl, farnesyl, and geranylgeranyl pyrophosphate have been prepared. Horner-Wadsworth-Emmons condensation of different terpene aldehydes with an unsymmetrical bisphosphonate was the key step in syntheses of the phosphonates bearing α,β-unsaturated acyloxy groups. After preparation of the respective phosphonic acids through reaction with TMSBr, both acids and esters were tested for their effects on DNA synthesis in human-derived myeloid and lymphoid leukemia cell lines. The phosphonate esters varied substantially in their ability to impair proliferation of the different cell lines, but testing against one possible target, farnesyl protein transferase (FPTase), revealed little impact at concentrations ranging up to 10μM. Because the corresponding 2,3-dihydro compounds showed similar biological activity, conjugate addition would not appear to be involved in the toxicity. Copyright (C) 2000 Elsevier Science Ltd.
UR - http://www.scopus.com/inward/record.url?scp=0033730313&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033730313&partnerID=8YFLogxK
U2 - 10.1016/S0968-0896(00)00212-1
DO - 10.1016/S0968-0896(00)00212-1
M3 - Article
C2 - 11131164
AN - SCOPUS:0033730313
VL - 8
SP - 2729
EP - 2737
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 12
ER -