TY - JOUR
T1 - Activity of nitrogen-containing and non-nitrogen-containing bisphosphonates on tumor cell lines
AU - Zhang, Yonghui
AU - Leon, Annette
AU - Song, Yongcheng
AU - Studer, Danielle
AU - Haase, Christa
AU - Koscielski, Lukasz A.
AU - Oldfield, Eric
PY - 2006/9/21
Y1 - 2006/9/21
N2 - We synthesized and tested three series of bisphosphonates for their activity in inhibiting the growth of three human tumor cell lines: MCF-7 (breast), NCI-H460 (lung), and SF-268 (CNS). The first series of compounds consisted of 49 nitrogen-containing bisphosphonates, the most active species being a tetrakispivaloyloxymethyl (POM) ester, having an (average) IC 50 of 6.8 μM. The second series of compounds consisted of nine terphenylbisphosphonates, the most active species also being a POM ester, having an IC50 of 2.2 μM. The third series of compounds consisted of seven halogen or cyanophenylbisphosphonates, the most active species again being a POM ester, having an IC50 of 500 nM. Taken together, these results are of interest because they show that bisphosphonate esters can have potent activity against a variety of tumor cell lines, with the most active terphenyl- and halophenyl-containing species having IC50 values ∼10-40x lower than the most potent commercially available bisphosphonates.
AB - We synthesized and tested three series of bisphosphonates for their activity in inhibiting the growth of three human tumor cell lines: MCF-7 (breast), NCI-H460 (lung), and SF-268 (CNS). The first series of compounds consisted of 49 nitrogen-containing bisphosphonates, the most active species being a tetrakispivaloyloxymethyl (POM) ester, having an (average) IC 50 of 6.8 μM. The second series of compounds consisted of nine terphenylbisphosphonates, the most active species also being a POM ester, having an IC50 of 2.2 μM. The third series of compounds consisted of seven halogen or cyanophenylbisphosphonates, the most active species again being a POM ester, having an IC50 of 500 nM. Taken together, these results are of interest because they show that bisphosphonate esters can have potent activity against a variety of tumor cell lines, with the most active terphenyl- and halophenyl-containing species having IC50 values ∼10-40x lower than the most potent commercially available bisphosphonates.
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U2 - 10.1021/jm060280e
DO - 10.1021/jm060280e
M3 - Article
C2 - 16970405
AN - SCOPUS:33748861780
SN - 0022-2623
VL - 49
SP - 5804
EP - 5814
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 19
ER -