کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1365419 | 981560 | 2008 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Chemotherapeutic bone-targeted bisphosphonate prodrugs with hydrolytic mode of activation Chemotherapeutic bone-targeted bisphosphonate prodrugs with hydrolytic mode of activation](/preview/png/1365419.png)
Osseous tissues are considered to be limited as therapeutic target sites due to their biological properties. We have designed and synthesized two kinds of hydrolytically activated chemotherapeutic prodrugs containing bisphosphonate, a bone-targeting moiety. The first can be conjugated to drug molecules with an available hydroxy group; the drug is attached to the bisphosphonate component through an ester-labile linkage. The second is for use with drug molecules with amine functional group. In this case, a self-immolative linker is used to attach the drug to the bisphosphonate component through a carbonate-labile linkage. The concept was demonstrated using the drugs camptothecin, which has a hydroxy functional group, and tryptophan, which is a model molecule for a drug with amine functionality. Both prodrugs showed significant binding capability to hydroxyapatite, the major component of bone, and were hydrolytically activated under physiological conditions.
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Journal: Bioorganic & Medicinal Chemistry Letters - Volume 18, Issue 2, 15 January 2008, Pages 816–820