Synthesis of isoprenoid bisphosphonate ethers through C-P bond formations

Potential inhibitors of geranylgeranyl diphosphate synthase

Xiang Zhou, Jacqueline E. Reilly, Kathleen A. Loerch, Raymond Hohl, David F. Wiemer

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

A set of bisphosphonate ethers has been prepared through sequential phosphonylation and alkylation of monophosphonate ethers. After formation of the corresponding phosphonic acid salts, these compounds were tested for their ability to inhibit the enzyme geranylgeranyl diphosphate synthase (GGDPS). Five of the new compounds show IC50 values of less than 1 μM against GGDPS with little to no activity against the related enzyme farnesyl diphosphate synthase (FDPS). The most active compound displayed an IC50 value of 82 nM when assayed with GGDPS, and no activity against FDPS even at a 10 μM concentration.

Original languageEnglish (US)
Pages (from-to)1645-1650
Number of pages6
JournalBeilstein Journal of Organic Chemistry
Volume10
DOIs
StatePublished - Jul 18 2014

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Farnesyltranstransferase
Ethers
Terpenes
Diphosphonates
Geranyltranstransferase
Alkylation
Enzymes
Salts

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

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title = "Synthesis of isoprenoid bisphosphonate ethers through C-P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase",
abstract = "A set of bisphosphonate ethers has been prepared through sequential phosphonylation and alkylation of monophosphonate ethers. After formation of the corresponding phosphonic acid salts, these compounds were tested for their ability to inhibit the enzyme geranylgeranyl diphosphate synthase (GGDPS). Five of the new compounds show IC50 values of less than 1 μM against GGDPS with little to no activity against the related enzyme farnesyl diphosphate synthase (FDPS). The most active compound displayed an IC50 value of 82 nM when assayed with GGDPS, and no activity against FDPS even at a 10 μM concentration.",
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Synthesis of isoprenoid bisphosphonate ethers through C-P bond formations : Potential inhibitors of geranylgeranyl diphosphate synthase. / Zhou, Xiang; Reilly, Jacqueline E.; Loerch, Kathleen A.; Hohl, Raymond; Wiemer, David F.

In: Beilstein Journal of Organic Chemistry, Vol. 10, 18.07.2014, p. 1645-1650.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synthesis of isoprenoid bisphosphonate ethers through C-P bond formations

T2 - Potential inhibitors of geranylgeranyl diphosphate synthase

AU - Zhou, Xiang

AU - Reilly, Jacqueline E.

AU - Loerch, Kathleen A.

AU - Hohl, Raymond

AU - Wiemer, David F.

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AB - A set of bisphosphonate ethers has been prepared through sequential phosphonylation and alkylation of monophosphonate ethers. After formation of the corresponding phosphonic acid salts, these compounds were tested for their ability to inhibit the enzyme geranylgeranyl diphosphate synthase (GGDPS). Five of the new compounds show IC50 values of less than 1 μM against GGDPS with little to no activity against the related enzyme farnesyl diphosphate synthase (FDPS). The most active compound displayed an IC50 value of 82 nM when assayed with GGDPS, and no activity against FDPS even at a 10 μM concentration.

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