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Activity of Nitrogen-Containing and Non-Nitrogen-Containing Bisphosphonates on Tumor Cell Lines

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journal contribution
posted on 21.09.2006, 00:00 by Yonghui Zhang, Annette Leon, Yongcheng Song, Danielle Studer, Christa Haase, Lukasz A. Koscielski, Eric Oldfield
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) IC50 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 ∼10−40× lower than the most potent commercially available bisphosphonates.